Genetic counseling

duce the burden of genetic disease, especially in populations in which specific diseases are common. Although generally performed for severe, untreatable disorders, 3 carrier screening for less serious yet prevalent conditions is also possible, but there is little information on its implications, even though it is likely to become more common. We propose that carrier screening for type 1 Gaucher disease (GD) exemplifies screening for a low-penetrance disease and present the results of the Israeli screening program. Carrier testing for diseases common in Ashkenazi Jews has been offered for over a decade, following the success of Tay-Sachs screening, which was initiated in the 1970s and has reduced the incidence of this lethal disease by 90%. The Ashkenazi Jewish screening panel has since expanded continuously. Testing for cystic fibrosis and GD has been offered in New York since 1994 5 and in Israel since 1995. Canavan disease, familial dysautonomia, and rarer diseases (eg, Fanconi anemia and Bloom syndrome) See also p 1329 and Patient Page. The aim of carrier screening is to prevent severe, untreatable genetic disease by identifying couples at risk before the birth of an affected child, and providing such couples with options for reproductive outcomes for affected pregnancies. Gaucher disease (GD) is an autosomal recessive storage disorder, relatively frequent in Ashkenazi Jews. Carrier screening for GD is controversial because common type 1 GD is often asymptomatic and effective treatment exists. However, screening is offered to Ashkenazi Jews worldwide and has been offered in Israel since 1995. Objective To examine the scope and outcomes of nationwide GD screening. Design, Setting, and Participants All Israeli genetic centers provided data on the number of individuals screened for GD, the number of carriers identified, the number of carrier couples identified, and the mutations identified in these couples between January 1, 1995, and March 31, 2003. Carrier couples were interviewed via telephone between January 21, 2003, and August 31, 2004, using a structured questionnaire for relevant outcome measures. Screening scope (number of testing centers, tested individuals, and carrier couples), screening process (type of pretest and posttest consultations), and screening outcomes (utilization of prenatal diagnosis and pregnancy terminations).

Waardenburg syndrome is an autosomal dominant disorder often characterised by pigmentary anomalies of skin and hair and various defects of neural crest tissues. It accounts for 1-3% of all cases of congenital deafness. Here we describe two siblings, congenitally mute and deaf with heterochromia irides. Case I; is one and half year old male with complete heterochromia irides and associated Hirschprung's disease. Case II is seven year old female with bilateral partial heterochromia irides.

Purpose Due to the increasing application of genome analysis and interpretation in medical disciplines, professionals require adequate education. Here, we present the implementation of personal genotyping as an educational tool in two genomics courses targeting Digital Health students at the Hasso Plattner Institute (HPI) and medical students at the Technical University of Munich (TUM). Methods We compared and evaluated the courses and the students’ perceptions on the course setup using questionnaires. Results During the course, students changed their attitudes towards genotyping (HPI: 79% [15 of 19], TUM: 47% [25 of 53]). Predominantly, students became more critical of personal genotyping (HPI: 73% [11 of 15], TUM: 72% [18 of 25]) and most students stated that genetic analyses should not be allowed without genetic counseling (HPI: 79% [15 of 19], TUM: 70% [37 of 53]). Students found the personal genotyping component useful (HPI: 89% [17 of 19], TUM: 92% [49 of 53]) and recommended ...

Purpose Due to the increasing application of genome analysis and interpretation in medical disciplines, professionals require adequate education. Here, we present the implementation of personal genotyping as an educational tool in two genomics courses targeting Digital Health students at the Hasso Plattner Institute (HPI) and medical students at the Technical University of Munich (TUM). We compared and evaluated the courses and the students' perceptions on the course setup using questionnaires. During the course, students changed their attitudes towards genotyping (HPI: 79% [15 of 19], TUM: 47% [25 of 53]). Predominantly, students became more critical of personal genotyping (HPI: 73% [11 of 15], TUM: 72% [18 of 25]) and most students stated that genetic analyses should not be allowed without genetic counseling (HPI: 79% [15 of 19], TUM: 70% [37 of 53]). Students found the personal genotyping component useful (HPI: 89% [17 of 19], TUM: 92% [49 of 53]) and recommended its inclusion in future courses (HPI: 95% [18 of 19], TUM: 98% [52 of 53]). Students perceived the personal genotyping component as valuable in the described genomics courses. The implementation described here can serve as an example for future courses in Europe.

RESUMEN: Durante el período comprendido desde octubre de 1996 hasta abril de 1999 se realizaron un total de 1 191 estudios cromosómicos prenatales. La indicación más frecuente fue la avanzada edad materna (70,36 % del total de casos). Se diagnosticaron 47 fetos ...

La depresión es una afectación del estado de ánimo caracterizada por sentimientos negativos como la tristeza, la desilusión, la frustración, la desesperanza, la inutilidad y la infelicidad, constituye un serio problema de salud y es la primera causa de discapacidad por enfermedades mentales. En la presente investigación se realizó un estudio de corte transversal, analítico, no experimental con casos y controles, en el período de Noviembre de 2011 a Octubre de 2012, con el objetivo de identificar las actitudes hacia la depresión, los estudios predictivos y las investigaciones genéticas, en individuos con la enfermedad, sus familiares, estudiantes y profesionales para luego diseñar una estrategia preventiva de asesoramiento genético para la depresión en el municipio de Pinar del Río. La muestra quedó constituida por 100 individuos; 30 pacientes, un familiar sano por cada uno de ellos, 20 estudiantes de medicina y profesionales de la salud respectivamente. Se aplicó un cuestionario validado en Cuba y Dinamarca, previo consentimiento informado. Se observó como resultado un mayor conocimiento de la depresión por estudiantes y profesionales, mientras que los pacientes y profesionales mostraron tener mayor conocimiento sobre las investigaciones genéticas. Los que mejor actitud tuvieron frente a los estudios genéticos, predictivos y prenatales fueron los profesionales. Se diseñó una estrategia de asesoramiento genético acorde a las características clínicas y sociodemográficas de los encuestados para ser aplicada en el área de salud. Palabras clave: Ética y genética, pruebas predictivas, genética psiquiátrica, depresión, estudios genéticos.

Aim: To explore the genetic cause of autosomal recessive retinitis pigmentosa in consanguineous families. Methods: The multi-centre study was conducted from July 2015 to June 2018 at Liaquat University of Medical and health Sciences, Jamshoro, the University of Sindh, Jamshoro, and Islamia University, Bahawalpur, Pakistan, and comprised families affected with non-syndromic autosomal recessive retinitis pigmentosa. Ophthalmological investigations were done to assess the fundus of the patients and the status of the disease. Pedigrees were drawn and family histories were recorded to find out the mode of inheritance. A 10cc sample of whole blood was obtained from each participant and deoxyribonucleic acid was extracted. Homozygosity mapping was performed using three short tandem repeat polymorphisms closely linked to phosphodiesterase 6A gene, and the linked families were Sanger-sequenced for identification of the mutation. Bioinformatic tools were used to design amplification refractor...

Unstable mutations, new challenges for genetic counseling of inherited disorders. Unstable mutations or amplification of DNA tandem repeats sequences constitute a new kind of genetic alteration discovered in the 90´s that cause hereditary diseases. This mutation has been found inside or near important genes involved in the normal neurological function in human beings. In some cases, the presence of the amplification causes altered expression of the genes, their inactivation or the synthesis of a protein with new functions. Some common characteristics of these diseases are that they affect the central nervous system and are degenerative in nature. Most of them show genetic anticipation meaning that the severity of the manifestations increases in each generation and appear at an earlier age. In most cases, the severity of the symptoms is positively correlated with the size of the amplification. Twenty illnesses caused by this kind of mutations have been identified so far. Briefly, this work reviews the current knowledge about this topic. Rev. Biol. Trop. 52(3): 491-499. Epub 2004 Dic 15.

Through-space charge transfer (TSCT) has been proven effective for designing thermally activated delayed fluorescence (TADF) emitters due to the separation of the frontier molecular orbitals. Although tuning of the interaction between the donor and acceptor by controlling the conformation is known to be crucial for the photophysical properties of TSCT excited states, it remains a challenge to realize efficient red and deep-red emissions. Herein, we designed two TSCT molecules, namely TPXZ-QX and TPXZ-2QX, by using oxygenbridged triphenylamine (TPXZ) as the electron donor with enhanced planarity and electron-donating capability. With a face-to-face orientation of the donor and acceptor segments and close p-p contacts, the new emitters have strong intramolecular noncovalent donor-acceptor interactions. The emissions of TPXZ-QX and TPXZ-2QX in doped thin films lie in the red (l max = 632 nm) to deep-red (l max = 665 nm) region. The photoluminescence quantum yields are 41% and 32% for TPXZ-QX and TPXZ-2QX, respectively. Organic light-emitting diodes (OLEDs) based on TPXZ-QX and TPXZ-2QX show external quantum efficiencies (EQEs) of up to 13.8% and 11.4%, respectively. This work indicates that the modulation of TSCT excited states based on strong intramolecular cofacial p-stacking interactions is a viable choice for the development of high-efficiency long-wavelength TADF emitters.

Counselling in cancer genetics may differ from genetic counselling in cancer. Cancer risk counsellors must provide patient education, risk assessment, pre-and post-test counselling, and intervention planning. In this complex multistep process, Contegiacomo et al. [1] favour the central role of the oncologist. Yet in many countries, including Italy, cancer genetic counselling is performed by trained clinical geneticists [2, 3]. It is our opinion that no matter who is the cancer genetic counsellor, some points must be addressed clearly. In the proposed multistep model, pedigree construction is performed only as a second step (T1), after an extensive information/education session (T0). We believe that the inclusion in a genetic risk assessment model should be performed only after collection of an accurate personal and familial history, rather than as a second step, after extensive information and education to the patient, because 'collecting genetic information is the first and most important step in genetic counselling ' [4]. Why should we extensively inform consultants about hereditary, familial and sporadic forms of cancer, available methods for risk assessment, implication of cancer risk, strategies for risk management, surveillance and prevention before knowing whether they have a cancer risk other than the normal population? General information about common risk factors for cancer development is provided through easy-to-read papers, pamphlets, educational websites and so on through Regional Health Services, while pedigree drawing is the way to collect relevant clinical history in a specific condition, and is the essential step with which to begin any genetic counselling. Cancer genetic counselling is now offered not only in a research project framework, but also as a medical practice in several clinical settings where other inherited late-onset conditions, with similar or more critical psychological impact, are followed. Finally, the statement that 'a low cognitive level and psychological distress preclude continuation of counselling' cannot be accepted in a genetic counselling setting. In our opinion, the patient's psychological distress should not preclude the practice of genetic counselling. The impact of psychological distress in counselling was analysed by psychologists involved in presymptomatic testing of lateonset disorders and is regarded as a part of the process of decision-making. DudokdeWit et al. [5] showed that risk carriers of late-onset diseases with higher stress scores may be actively dealing with the emotional implications of the test, whereas those with low stress scores may be unable to face these implications. Therefore, it seems important to identify the patient's strategy of coping with the potential threat, in order to provide suitable counselling and necessary guidance.

Cerebral cavernous malformations (CCM) are vascular malformations that can occur as a sporadic or a familial autosomal dominant disorder. Clinical and cerebral MRI data on large series of patients with a genetic form of the disease are now available. In addition, three CCM genes have been identifi ed: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. These recent developments in clinical and molecular genetics have given us useful information about clinical care and genetic counselling and have broadened our understanding of the mechanisms of this disorder.

Purpose of Review This review uses clinical cases to highlight some of the ethical dilemmas currently faced by oncologists, geneticists and others who request genetic testing for inherited cancer disorders. Recent Findings Recent ethical guidance supports clinicians in testing patients when other family members decline similar testing, even when such testing will reveal those family members' genetic status. And increasingly there is acknowledgement that when a patient declines to share genetic results with family members, clinicians may have an ethical duty to breach patient confidentiality in order to inform at-risk relatives to whom they may owe a duty of care, so that they can choose to access genetic testing and potentially life-saving screening and treatment. Summary Genetic testing for inherited cancer disorders raises multiple ethical issues, which cannot always be easily resolved by discussion with patients, or with their family members. Clinical ethics committees can provide valuable assistance in resolving the dilemmas presented in these cases. Cancer . Predictive genetic testing . Confidentiality . Duty of care . Ethics JK is Secretary of the St George's Clinical Ethics Committee. NE is Chairman of the St George's Clinical Ethics Committee. We do not discuss whether there can or should be, in some cases, a legal duty to disclose genetic information to some relatives against the wishes of the patient. This article is part of the Topical Collection on Cancer Genomics

Mutations in the LDLR gene are associated with autosomal co-dominant Familial Hypercholesterolaemia (FH). Our current LDLR gene screening service includes a combination of high resolution melting analysis and DNA sequencing for highly polymorphic exons, followed by MLPA testing for large deletions and duplications. In a high percentage of individuals with clinically indicated FH a mutation is not identified. To increase the intron coverage of our routine LDLR screening test and also to assess the function of novel potentially pathogenic splicing variations, we developed a functional pre-mRNA screening test. There are varied estimates of the percentage of inherited disease states caused by mutations that alter splicing, although more recently they have been estimated at up to 50 to 60%. Traditionally, mutations affecting the consensus splice-sites have been identified easily during routine screening which includes the intron/exon boundary. However, deeper intronic or even exonic mutations that play a role in splicing often go undetected. The intronic and non-coding regions of the LDLR gene cover some 44 kb, and although possible to sequence, we explored a faster, less laborious technique that would identify functional splicing errors in vivo. We amplified several overlapping cDNA fragments, and used fragment analysis to identify aberrant sized products. This method was used to characterise several mutations identified during our routine LDLR gene testing and also identified a number of new variants that had not been detected by the routine diagnostic test. The amount of aberrant pre-mRNA splicing detected was lower than expected, however, we felt this method was a great addition to our current testing pathway and is particularly useful for characterising novel potentially pathogenic splicing variations.

Purpose of Review This review uses clinical cases to highlight some of the ethical dilemmas currently faced by oncologists, geneticists and others who request genetic testing for inherited cancer disorders. Recent Findings Recent ethical guidance supports clinicians in testing patients when other family members decline similar testing, even when such testing will reveal those family members’ genetic status. And increasingly there is acknowledgement that when a patient declines to share genetic results with family members, clinicians may have an ethical duty to breach patient confidentiality in order to inform at-risk relatives to whom they may owe a duty of care, so that they can choose to access genetic testing and potentially life-saving screening and treatment. Summary Genetic testing for inherited cancer disorders raises multiple ethical issues, which cannot always be easily resolved by discussion with patients, or with their family members. Clinical ethics committees can provid...

Purpose: The purpose of this study is to analyze the survival rate of patients with metastatic breast cancer according to the location of metastases and to identify factors related to survival in these patients. Methods: The data of 184 patients who were treated for metastatic breast cancer at the Cumhuriyet University Oncology Center between 2006 and 2013 were retrospectively reviewed. Results: One hundred eighty-one patients (98%) in the study were female and three were male (2%). The median age at diagnosis was 51 years (range: 18-83 years). Following development of the first metastasis, median survival of the patients was 27 months (1-177 months), two-year survival was 55%, and five-year survival was 27%. The longest survival duration was in the patients with bone metastases, and the shortest survival was noted in patients with brain metastases. Age, menopausal status, diabetes mellitus, performance status, number of metastases (single organ vs. multiple organs), localization of...

Balanced reciprocal translocations associated with genetic disorders have facilitated the identification of a variety of genes for early-onset monogenic disorders, but only rarely the genes associated with common and complex disorders. To assess the potential of chromosomal breakpoints associated with common/ complex disorders, we investigated the full spectrum of diseases in 731 carriers of balanced reciprocal translocations without known early-onset disorders in a nation-wide questionnaire-based re-examination. In 42 families, one of the breakpoints at the cytogenetic level concurred with known linkage data and/or the translocation co-segregated with the reported phenotype, for example, we found a significant linkage (lod score ¼ 2.1) of dyslexia and a co-segregating translocation with a breakpoint in a previously confirmed locus for dyslexia. Furthermore, we identified 441 instances of at least two unrelated carriers with concordant breakpoints and traits. If applied to other populations, re-examination of translocation carriers may identify additional genotype -phenotype associations, some of which may be novel and others that may coincide with and provide additional support of data presented here.

PurposeAn accurate evaluation of the penetrance of BRCA1 and BRCA2 mutations is essential to the identification and clinical management of families at high risk of breast and ovarian cancer. Existing studies have focused on Ashkenazi Jews (AJ) or on families from outside the United States. In this article, we consider the US population using the largest US-based cohort to date of both AJ and non-AJ families.MethodsWe collected 676 AJ families and 1,272 families of other ethnicities through the Cancer Genetics Network. Two hundred eighty-two AJ families were population based, whereas the remainder was collected through counseling clinics. We used a retrospective likelihood approach to correct for bias induced by oversampling of participants with a positive family history. Our approach takes full advantage of detailed family history information and the Mendelian transmission of mutated alleles in the family.ResultsIn the US population, the estimated cumulative breast cancer risk at ag...

Background-Deleterious mutations of the BRCA1 and BRCA2 genes confer susceptibility to breast and ovarian cancer. At least 7 models for estimating the probabilities of having a mutation are used widely in clinical and scientific activities; however, the merits and limitations of these models are not fully understood. Objective-To systematically quantify the accuracy of the following publicly available models to predict mutation carrier status: BRCAPRO, family history assessment tool, Finnish, Myriad

BACKGROUND: The hereditary form of medullary thyroid carcinoma may occur isolated as a familial medullary thyroid carcinoma (FMTC) or as part of Multiple Endocrine Neoplasia 2A (MEN2A) and 2B (MEN2B). MEN2B is a rare syndrome, its phenotype may usually, but not always, be noted by the physician. In the infant none of the MEN2B characteristics are present, except by early gastrointestinal dysfunction caused by intestinal neuromas. When available, genetic analysis confirms the diagnosis and guides pre-operative evaluation and extent of surgery. Here we report four cases of MEN2B in which the late diagnosis had a significant impact in clinical evolution and, potentially, in overall survival. CASE REPORT: We report four cases, 2 men and 2 women, with differences in their phenotypes and with a late diagnosis. The first case has a history of severe gastrointestinal obstruction requiring a surgery intervention two days after his birth. The second told had nodules in the oral mucosa and con...

La coyuntura actual nos ha demostrado una vez más la necesidad
de construir una bioética global que, junto a otras herramientas como son
los derechos humanos, contribuya a la protección integral de la persona en
todos sus niveles. El objetivo del presente artículo consiste en realizar una
primera propuesta de sustento teórico y de principios de una bioética global
personalista a partir de la matriz filosófica del personalismo comunitarista.

The trisomy 18 syndrome, also known as Edwards syndrome, is a common chromosomal disorder due to the presence of an extra chromosome 18, either full, mosaic trisomy, or partial trisomy 18q. The condition is the second most common autosomal trisomy syndrome after trisomy 21. The live born prevalence is estimated as 1/6,000-1/8,000, but the overall prevalence is higher (1/2500-1/2600) due to the high frequency of fetal loss and pregnancy termination after prenatal diagnosis. The prevalence of trisomy 18 rises with the increasing maternal age. The recurrence risk for a family with a child with full trisomy 18 is about 1%. Currently most cases of trisomy 18 are prenatally diagnosed, based on screening by maternal age, maternal serum marker screening, or detection of sonographic abnormalities (e.g., increased nuchal translucency thickness, growth retardation, choroid plexus cyst, overlapping of fingers, and congenital heart defects ). The recognizable syndrome pattern consists of major and minor anomalies, prenatal and postnatal growth deficiency, an increased risk of neonatal and infant mortality, and marked psychomotor and cognitive disability. Typical minor anomalies include characteristic craniofacial features, clenched fist with overriding fingers, small fingernails, underdeveloped thumbs, and short sternum. The presence of major malformations is common, and the most frequent are heart and kidney anomalies. Feeding problems occur consistently and may require enteral nutrition. Despite the well known infant mortality, approximately 50% of babies with trisomy 18 live longer than 1 week and about 5-10% of children beyond the first year. The major causes of death include central apnea, cardiac failure due to cardiac malformations, respiratory insufficiency due to hypoventilation, aspiration, or upper airway obstruction and, likely, the combination of these and other factors (including decisions regarding aggressive care). Upper airway obstruction is likely more common than previously realized and should be investigated when full care is opted by the family and medical team. The complexity and the severity of the clinical presentation at birth and the high neonatal and infant mortality make the perinatal and neonatal management of babies with trisomy 18 particularly challenging, controversial, and unique among multiple congenital anomaly syndromes. Health supervision should be diligent, especially in the first 12 months of life, and can require multiple pediatric and specialist evaluations. Trisomy 18, Edwards syndrome

Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions, resulting in discordance between an individual's sex chromosomes, gonads, and/or anatomic sex. The management of a newborn with suspected 46,XY DSD remains challenging. Newborns with 46,XY DSD may present with several phenotypes ranging from babies with atypical genitalia or girls with inguinal herniae to boys with micropenis and cryptorchidism. A mismatch between prenatal karyotype and female phenotype is an increasing reason for presentation. Gender assignment should be avoided prior to expert evaluation and possibly until molecular diagnosis. The classic diagnostic approach is time and cost-consuming. Today, a different approach may be considered. The first line of investigations must exclude rare life-threatening diseases related to salt wasting crises. Then, the new genetic tests should be performed, yielding increased diagnostic performance. Focused imaging or endocrine studies should be performed on the basis of genetic results in order to reduce repeated and invasive investigations for a small baby. The challenge for health professionals will lie in integrating specific genetic information with better defined clinical and endocrine phenotypes and in terms of long-term evolution. Such advances will permit optimization of counseling of parents and sex assignment. In this regard, society has significantly changed its attitude to the acceptance and expansion beyond strict binary male and female sexes, at least in some countries or cultures. These management advances should result in better personalized care and better long-term quality of life of babies born with 46,XY DSD.

Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions, resulting in discordance between an individual's sex chromosomes, gonads, and/or anatomic sex. The management of a newborn with suspected 46,XY DSD remains challenging. Newborns with 46,XY DSD may present with several phenotypes ranging from babies with atypical genitalia or girls with inguinal herniae to boys with micropenis and cryptorchidism. A mismatch between prenatal karyotype and female phenotype is an increasing reason for presentation. Gender assignment should be avoided prior to expert evaluation and possibly until molecular diagnosis. The classic diagnostic approach is time and cost-consuming. Today, a different approach may be considered. The first line of investigations must exclude rare life-threatening diseases related to salt wasting crises. Then, the new genetic tests should be performed, yielding increased diagnostic performance. Focused imaging or endocrine studi...

Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein ( AIP ) gene cause pituitary adenoma predisposition (PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. Typically, PAP patients were of a young age at diagnosis but did not display a strong family history of pituitary adenomas. To evaluate the role of AIP in pituitary adenoma susceptibility in other populations and to gain insight into patient selection for molecular screening of the condition, we investigated the possible contribution of AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition pat...

El cáncer considerado como un problema creciente de salud pública. Caracterizado por los altos costos derivados por los múltiples procedimientos de tipo diagnóstico y de tratamientos. Dependiendo del estadio de la enfermedad resultan en algunos casos poco efectivos y desesperanzadores, esto obliga a las instituciones a instaurar medidas de contención y mejoramiento continuo para disminuir el impacto negativo en el paciente y los problemas que pueden generar en los sistemas de atención en salud.
En el texto mostramos como la creación de un programa de atención integral en salud para los pacientes con cáncer, mejora procesos como la detección temprana y la implementación de tratamientos médicos y quirúrgicos de manera oportuna, creando y definiendo las rutas de atención efectivas e implementando una política de eliminación de “barreras” que dificultan de manera importante una intervención adecuada y oportuna.
El hospital San juan de Dios, institución de mediana complejidad de atención, creó el Consultorio Rosado para organizar e integrar la atención de los pacientes, con un enfoque inicial en cáncer mamario pero que con el tiempo se extendió a todos los cánceres. Exponemos como es la experiencia en este programa de atención, que a pesar de ser privado, se articula con el sector público para su funcionamiento. Se muestran los resultados basados en los indicadores de gestión de calidad y las ventajas, la diferentes amenazas, fortalezas, debilidades y oportunidades. También como se debería proyectar en un futuro para garantizar la sostenibilidad y el mejoramiento continuo.

Discussion of family health history (FH) has the potential to be a communication tool within families and with health providers to stimulate health promotion related to many chronic conditions, including those with genetic implications for prevention, screening, diagnosis, treatment. Diverse communities with disparities in health outcomes may require different approaches to engage individuals and families in the evolving areas of genetic risk communication, assessment, and services. This work was a partnership of a local urban agency and academic genetics professionals to increase understanding of community concerns and preferences related to FH and genetic awareness. Thirty community stakeholders in the East Baltimore area participated in structured interviews conducted by community members. We identified key themes on family health history FH, risk assessment, and genetic services. Forty-three percent (18/27) of community stakeholders thought families in East Baltimore did not discuss family health history FH with doctors. Stakeholders recognized the benefits and challenges of potential actions based on genetic risk assessment and the multiple competing priorities of families. FH awareness with community engagement and genetics education were the major needs identified by the participants. Research undertaken in active collaboration with community partners can provide enhanced consumer perspectives on the importance of family health history and its potential connections to health promotion and prevention activities.

were assessed using cross tabulation, and both crude and adjusted odds ratios were calculated with a 95% confidence interval. Variables with p-values less than 0.05 were considered statistically significant. Results: A total of 161 HCPs participated in the study, comprising 69 (42.9%) females and 92 (57.1%) males. The majority of participants were nurses 105 (65%), followed by physicians 20 (12.4%), pharmacists 19 (11.8%), midwives 10 (6.2%), and health officers 7 (4.3%). More than half of the participants demonstrated inadequate knowledge 94 (58.4%), negative attitudes 82 (50.9%), and poor practices 90 (55.9%) regarding the use of thiopurine drugs for the treatment of ALL. Approximately 50 (31.1%) participants understood the term "thiopurine drugs," while 89 (55.3%) were aware of their adverse drug reactions. However, the majority 136 (84.5%) had not received training on how to report adverse drug reactions. Conclusion: The majority of healthcare professionals demonstrated negative attitudes, inadequate knowledge, and poor practices concerning the reporting of adverse drug reactions associated with thiopurine drugs.

Autism is etiologically heterogeneous; medical conditions are implicated in only a minority of cases, whereas metabolic disorders are even less common. Recently, there have been articles describing the association of autism with mitochondrial abnormalities. We critically review the current literature and conclude that mitochondrial disorders are probably a rare and insignificant cause of pure autism; however, evidence is accumulating that both autosomal recessive and maternally inherited mitochondrial disorders can present with autistic features. Most patients will present with multisystem abnormalities associated with autistic behavior. Finding biochemical or structural mitochondrial abnormalities in an autistic child does not necessarily imply a primary mitochondrial disorder but can also be secondary to technical inaccuracies or another genetic disorder. Clinicians should be careful in diagnosing a mitochondrial disorder in an autistic child because it has important implications ...

The 22q11.2 deletion syndrome is the most frequent human microdeletion syndrome. The phenotype is highly variable, being characterized by conotruncal heart defect, facial dysmorphisms, velopharyngeal insufficiency, learning difficulties and mental retardation. The objective of this study was to investigate the frequency of deletion 22q11.2 in a Brazilian sample of individuals with isolated conotruncal heart defect and 22q11.2 deletion syndrome phenotype. Twenty-nine patients were studied by classical cytogenetics, by fluorescence in situ hybridization (FISH), and by molecular techniques. Cytogenetic analysis by G-banding revealed a normal karyotype in all patients except one who presented a 47,XX,+idic(22)(q11.2) karyotype. Using molecular techniques, a deletion was observed in 25% of the patients, all exhibiting a 22q11.2 deletion syndrome phenotype. In none of the cases the deletion was inherited from the parents. The frequency of 22q11.2 deletion was higher in patients with the c...

Purpose: To determine the frequency of genetic alterations in a population of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia. Materials and Methods: Retrospective study of a group of 143 infertile men with severe oligozoospermia or non-obstructive azoospermia from the Andrology Outpatient Clinic of the Human Reproduction Service at the ABC School of Medicine. Of these patients, 100 had severe oligozoospermia, and 43 non-obstructive azoospermia. All patients underwent a genetic study which included karyotype analysis and Y-microdeletion investigation. Results: Genetic abnormalities were found in 18.8% of the studied patients. Chromosomal abnormalities were found in 6.2% of the patients, being more prevalent in the azoospermia group (11.6%) than in the oligozoospermia group (4%). Chromosomal variants were found in 8.3%, and Y-chromosome microdeletions in 4.2% of patients. The high frequency of genetic alterations (18.8%) in our series justified performing a genetic investigation in a population with idiopathic infertility, as results may help determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations such as genetic male infertility, mental retardation, genital ambiguity and/or birth defects.

Mosaicism, an important cause for recurrent T21, should be suspected in families with more than one affected child wishing to receive prenatal counseling. Fluorescence in-situ hybridization analysis in a large number of cells and in different tissue samples is critical for detecting low-level mosaicism and is a key prognostic factor.

Abstract: The Estonian population-based biobank, with 52,000 participants ’ genetic and health data, is the largest epidemiological cohort in the Baltic region. Participants were recruited through a network of medical professionals throughout Estonia (population 1.34 million). Unique legislation as well as a broad consent form give the Estonian Genome Center, a research institute of the University of Tartu, permission to re-contact participants and to retrieve participants ’ data from national registries and databases. In addition to two re-contacting projects to update the health data of participants, extensive clinical characterizations have been retrieved from national registries and hospital databases regularly since 2010. Acquiring data from electronic health records and registries has provided a means to update and enhance the database of the Genome Center in a timely manner and at low cost. The resulting database allows a wide spectrum of genomic and epidemiological research ...

Prenatal Diagnosis (PND) forms an important part of primary preventive management for families having a child affected with primary immunodeficiency. Although individually sparse, collectively this group of genetic disorders represents a significant burden of disease. This paper discusses the prenatal services available for affected families at various centers across the country and the challenges and ethical considerations associated with genetic counseling. Mutation detection in the index case and analysis of chorionic villous sampling or amniocentesis remain the preferred procedures for PND and phenotypic analysis of cordocentesis sample is reserved for families with wellcharacterized index case seeking PND in the latter part of the second trimester of pregnancy. A total of 112 families were provided PND services in the last decade and the presence of an affected fetus was confirmed in 32 families. Post-test genetic counseling enabled the affected families to make an informed decision about the current pregnancy.

To assess the knowledge of nurses involved in the care of oncology patients in a public university hospital, regarding breast cancer and hereditary breast cancer, and to verify the use of such knowledge in their daily practice. This is a descriptive cross-sectional study. Data were obtained through a structured, self-administered questionnaire. Out of 154 nurses, 137 (88.9%) agreed to participate in the study. Two questionnaires were excluded such that 135 questionnaires were analyzed. The global percentage of correct answers was not associated with age (p=0.173) or degree/specialization (p=0.815). Questions were classified into categories. In categories involving knowledge of established breast cancer risk factors and indicators of hereditary breast cancer, the rate of correct answers was 65.8% and 66.4%, respectively. On the practice of genetic counseling, 40.7% of those interviewed were not sure about the definition of genetic counseling and 78.5% reported never having identified...

Background: Molecular genetic analysis is the only method that allows accurate detection of Cystic Fibrosis (CF) carriers. Nevertheless, its application is restricted to those families in which the affected child holds known mutations. Since most Chilean CF patients already studied are heterozygous and carry a mutation not yet characterized, direct identification of carriers is limited. Linkage analysis of Restriction Fragment Length Polymorphisms (RFLP), using DNA markers closely linked to the CFTR gene, is a useful tool for the detection of carriers in families in which the patient carries an unknown mutation. Aim: To emphasize the usefulness of KM19 and MetH markers for RFLP analysis in extended genealogies in order to identify carriers of unknown mutations. Material and Methods: Selection of three families, in which a sibling of an index case, identified as ∆F-508/unknown mutation, could not be identified as heterozygous carrier or a normal homozygous. Haplotypic characterization for KM19 and MetH markers was performed by PCR amplification of genomic DNA followed by allele specific restriction enzymatic digestion. Results: The siblings of two families were identified as carriers and the sibling of the third family was identified as normal. Conclusions: KM19 and MetH haplotypic analysis provided a rapid method for carrier detection in the families under study. The analysis may be used as a supplement to direct genetic diagnosis and be helpful in genetic counseling (

An 8months female child came to our Dept. of Paediatrics, M.K.C.G. Medical College, Berhampur, Odisha, India for evaluation of motor delay with history of cyanotic spell with features of Apert Syndrome. Apert syndrome is a rare type 1 acrocephalosyndactyly syndrome characterized by dysmorphic facial features, craniosynostosis and severe syndactyly of hands and feet. It represents an autosomal dominant inheritance and occurs due to the gene mutations in the receptors of the fibroblast growth factor 2(FGFR2).

The 5α‐reductase type 2 deficiency is a rare autosomal recessive 46,XY disorder of sex development caused by the mutated 5α‐reductase type 2 (SRD5A2) gene. In this disease, defective conversion of testosterone to dihydrotestosterone leads to variable presentations of male ambiguous genitalia during fetal development. The most crucial clinical decision for the affected individual is proper gender assignment; therefore, a prompt and correct diagnosis is important. In this present study, we report a normal male karyotype manifesting microphallus, bifid scrotum/labia majora with bilateral palpable gonads, and a blind‐ended pseudovagina. The mutation analysis of the SRD5A2 gene revealed one novel C to T transition changing glutamine to a stop codon at codon 71 (p.Q71X) in exon 1 and one known G to A transition changing arginine to glutamine at codon 227 (p.R227Q) in exon 4. The p.Q71X mutation presumably results in a truncated protein, while the p.R227Q mutation is conceived to impair en...

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%). The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on the phenotypic severity going from high mortality within the first year for SMA type 1 to no mortality for the chronic and later onset forms.

Cockayne's Syndrome (CS) is a rare autosomal recessive disorder characterized by deficiency in the transcription-couple DNA repair pathway caused by mutations in the genes ERCC6 in 65% of individuals and ERCC8 in 35% of individuals. Here we report a rare case of Cockayne's syndrome in a girl who presented with hallmark features specific to the syndrome. Dissemination of our knowledge about clinical manifestations encountered in Cockayne syndrome is instrumental not only for early evaluation and treatment to prolong life expectancy, but also to initiate early genetic counselling with parents concerning future pregnancies.