Ayberk Turkyilmaz1, Ceren Alavanda2, Esra Arslan Ates3, Bilgen Bilge Geckinli2, Hamza Polat2, Mehmet Gokcu4, Taner Karakaya5, Alper Han Cebi4, Mehmet Ali Soylemez2, Ahmet İlter Guney2, Pinar Ata2, Ahmet Arman2. 1. Department of Medical Genetics, School of Medicine, Karadeniz Technical University, Trabzon, Turkey. ayberkturkyilmaz@gmail.com. 2. Department of Medical Genetics, School of Medicine, Marmara University, Istanbul, Turkey. 3. Department of Medical Genetics, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey. 4. Department of Medical Genetics, School of Medicine, Karadeniz Technical University, Trabzon, Turkey. 5. Department of Medical Genetics, Isparta City Hospital, Isparta, Turkey.
Abstract
PURPOSE: Premature ovarian insufficiency (POI) is a heterogeneous disorder characterized by the cessation of menstrual cycles before the age of 40 years due to the depletion or dysfunction of the ovarian follicles. POI is a highly heterogeneous disease in terms of etiology. The aim of this study is to reveal the genetic etiology in POI patients. METHODS: A total of 35 patients (mean age: 27.2 years) from 28 different families diagnosed with POI were included in the study. Karyotype, FMR1 premutation analysis, single nucleotide polymorphism (SNP) array, and whole-exome sequencing (WES) were conducted to determine the genetic etiology of patients. RESULTS: A total of 35 patients with POI were first evaluated by karyotype analysis, and chromosomal anomaly was detected in three (8.5%) and FMR1 premutation was detected in six patients (17%) from two different families. A total of 29 patients without FMR1 premutation were included in the SNP array analysis, and one patient had a 337-kb deletion in the chromosome 6q26 region including PARK2 gene, which was thought to be associated with POI. Twenty-nine cases included in SNP array analysis were evaluated simultaneously with WES analysis, and genetic variant was detected in 55.1% (16/29). CONCLUSION: In the present study, rare novel variants were identified in genes known to be associated with POI, which contribute to the mutation spectrum. The effects of detected novel genes and variations on different pathways such as gonadal development, meiosis and DNA repair, or metabolism need to be investigated by experimental studies. Molecular etiology allows accurate genetic counseling to the patient and family as well as fertility planning.
PURPOSE: Premature ovarian insufficiency (POI) is a heterogeneous disorder characterized by the cessation of menstrual cycles before the age of 40 years due to the depletion or dysfunction of the ovarian follicles. POI is a highly heterogeneous disease in terms of etiology. The aim of this study is to reveal the genetic etiology in POI patients. METHODS: A total of 35 patients (mean age: 27.2 years) from 28 different families diagnosed with POI were included in the study. Karyotype, FMR1 premutation analysis, single nucleotide polymorphism (SNP) array, and whole-exome sequencing (WES) were conducted to determine the genetic etiology of patients. RESULTS: A total of 35 patients with POI were first evaluated by karyotype analysis, and chromosomal anomaly was detected in three (8.5%) and FMR1 premutation was detected in six patients (17%) from two different families. A total of 29 patients without FMR1 premutation were included in the SNP array analysis, and one patient had a 337-kb deletion in the chromosome 6q26 region including PARK2 gene, which was thought to be associated with POI. Twenty-nine cases included in SNP array analysis were evaluated simultaneously with WES analysis, and genetic variant was detected in 55.1% (16/29). CONCLUSION: In the present study, rare novel variants were identified in genes known to be associated with POI, which contribute to the mutation spectrum. The effects of detected novel genes and variations on different pathways such as gonadal development, meiosis and DNA repair, or metabolism need to be investigated by experimental studies. Molecular etiology allows accurate genetic counseling to the patient and family as well as fertility planning.
Authors: Elena J Tucker; Sonia R Grover; Gorjana Robevska; Jocelyn van den Bergen; Chloe Hanna; Andrew H Sinclair Journal: Eur J Hum Genet Date: 2018-04-30 Impact factor: 4.246
Authors: R Morales; B Lledo; J A Ortiz; F M Lozano; E M Garcia; A Bernabeu; A Fuentes; R Bernabeu Journal: J Assist Reprod Genet Date: 2022-10-08 Impact factor: 3.357