Background and Aims: The fragile X mental retardation 1 (FMR1) gene contains a CGG repeat sequenc... more Background and Aims: The fragile X mental retardation 1 (FMR1) gene contains a CGG repeat sequence within its 5'UTR, the expansion of which can result in both neurological and reproductive disorders. Repeats containing more than 200 CGG repeats are defined as a full mutation and cause fragile X syndrome. The repeat numbers between 55 and 200 CGG are defined as permutation (PM) and can cause premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR). Normal alleles have 5 to 44 repeats and intermediate 45 to 54 (IM). POI affects ~ 1% of women before the age of 40 and 0.1% before the age of 30. Twenty percent of women with POI can have the premutation of CGG repeat, which can expand to the full mutation in the following generations causing Fragile X syndrome with Intellectual disability. Therefore it is important to evaluate patients with POF for the presence of CGG repeats. The aim of this study is mutation detection and determination of expanded allele of the FMR1 CGG repeats using TRP PCR in four Iranian women from 29 to 34 years old. Material & Methods: Four women in the age range of 29-34 with premature ovarian insufficiency (POI) and idiopathic infertility after genetic counseling were referred to the Molecular Laboratory in the Department of Medical Genetics, Sarem Women's Hospital. DNA of whole blood samples was extracted using the saltingout method. Amplification of the FMR1 gene of every patient was performed by TRP PCR using automated capillary electrophoresis used for the detection of expended FMR1 alleles. Findings: CGG repeats sizing using TRP-PCR identified 3 women with PM allele, one was homozygote and two were heterozygote for PM allele. Another patient showed a heterozygote IM allele. Conclusion: In this study, the FMR1 gene PM alleles and also IM allele were associated with infertility. It is recommended that women with POI and Infertility of unknown etiology, and particularly those with a family history of POI, should be considered for the evaluation of CGG repeats.
Background and Objective: Consanguinity is defined as the marriage between close relatives. The d... more Background and Objective: Consanguinity is defined as the marriage between close relatives. The deleterious effects associated with consanguinity may be caused by the expression of rare recessive genes inherited from common ancestors. Consanguineous marriage is significantly higher in many genetic diseases leading to prenatal, neonatal, child morbidity or mortality. Consanguineous marriage is a common practice in the Middle East including Iran with a rate of 30-85%. The present study was undertaken to analyze the prevalence of chromosomal abnormality (CA) in patients with consanguineous marriages. Material & Methods: Standard Cytogenetics techniques were carried out on the peripheral blood of 1055 patients with consanguineous marriage. Chromosome analysis was carried out using GTG-banding technique. The patients were referred to the Cytogenetics laboratory of Sarem Women's hospital during 2006-2021. 969 patients were due to genetic counseling for consanguineous marriage and 86 patients with a referral of consanguineous marriage and other reasons comprising of the previous history of recurrent abortions, infertility, intellectual disability, expired child, stillbirth, and a child with chromosome abnormality. Findings: Chromosomal abnormalities were found in 34 patients (3.22%) out of a total of 1055 patients. Most of the abnormalities were structural (97 %). Chromosomal abnormalities were found in 15 females (44.1%) and 19 males (55.9%). Inversions were the most common chromosomal abnormalities (64.7 %) diagnosed in this study. Pericentric inversion around the centromere of chromosome 9 was observed in 18 cases (1.70 %). Chromosomal inversions were found in the heterochromatin region of chromosome 1 in one case and chromosome 2 in one other case. Paracentric inversion of chromosome 14 was found in one case. One patient had a pericentric inversion of large size in one chromosome 9. Robertsonian translocation was found in three patients. Five patients had reciprocal translocation between two chromosomes. One patient had insertion of an unknown chromosome material within the short arm of chromosome 3. Amongst patients with consanguineous marriage and other reasons, only those with recurrent abortions (3 abnormals) and infertility (1 abnormal) had chromosome abnormalities. Chromosome abnormality rate in individuals referred for consanguineous marriage genetic counseling was 3.09% compared to 4.65% in those referred for consanguineous marriage and recurrent abortions or infertility. Conclusion: Compared to the rate of chromosome abnormality in the general population of less than 1%, the 3.09% of chromosomal abnormalities rate in consanguineous marriages in this study is high. However, this rate is even higher in individuals with consanguineous marriage and a history of recurrent abortion or infertility, with 4.65%. Due to the high rate of consanguineous marriages in the Iranian population, genetic counseling and chromosome analysis in couples with consanguineous marriage is highly recommended.
Background and Objective: Infertility is a major health problem affecting 10-15% of couples globa... more Background and Objective: Infertility is a major health problem affecting 10-15% of couples globally. Genetic factors such as chromosomal abnormalities are one of the major causes of infertility and spontaneous abortions. The aim of this study was to establish the chromosome abnormality and chromosomal variants' rate amongst couples referred for reasons of infertility and subfertility to the Cytogenetics laboratory of Sarem Women's hospital in Tehran between 2006 and 2017. Material and methods: In this study, a total number of 6514 patients were referred for chromosomal investigation. The mean age of referral female and male patients were 30 and 34 years, respectively. Referral reasons included infertility, recurrent abortions, and unsuccessful Assisted Reproductive Technologies (ARTs). Heparinized peripheral blood was obtained. Cytogenetic investigation was carried out using standard techniques. GTG high resolution banding technique was used and 20-50 metaphase spreads were studied. CBG, NOR banding, and FISH investigation were carried out if necessary. Results: The overall chromosome abnormality rate was 5.28 percent (344 out of 6514). The cytogenetic results for these referral couples are as follows: 66 (19.1%) patients had a numerical chromosome abnormality including sex chromosomes and marker chromosomes. 120 (34.9%) patients had structural chromosome abnormalities. 158 (46%) patients had mosaicism with different cell lines.70 (1.07%) patients had an inversion of chromosome 9. Discussion and Conclusion: Cytogenetic investigation in patients with infertility and subfertility is critical as a first line genetic investigation. The findings of chromosome abnormality are of great value in the better management of the patients.
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