Article detail · 2019
Exome sequencing of a primary ovarian insufficiency cohort reveals common molecular etiologies for a spectrum of disease
Journal
The Journal of Clinical Endocrinology & MetabolismISSN 0021-972X
The ISSN points to another catalog journal; the name is from the YÖKSİS record.
- Year
- 2019
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue The Journal of Clinical Endocrinology & Metabolism
- Catalog match (ISSN) Journal of Clinical Endocrinology and Metabolism
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
CONTEXT: Primary ovarian insufficiency (POI) encompasses a spectrum of premature menopause, including both primary and secondary amenorrhea. For 75% to 90% of individuals with hypergonadotropic hypogonadism presenting as POI, the molecular etiology is unknown. Common etiologies include chromosomal abnormalities, environmental factors, and congenital disorders affecting ovarian development and function, as well as syndromic and nonsyndromic single gene disorders suggesting POI represents a complex trait. OBJECTIVE: To characterize the contribution of known disease genes to POI and identify molecular etiologies and biological underpinnings of POI. DESIGN, SETTING, AND PARTICIPANTS: We applied exome sequencing (ES) and family-based genomics to 42 affected female individuals from 36 unrelated Turkish families, including 31 with reported parental consanguinity. RESULTS: This analysis identified likely damaging, potentially contributing variants and molecular diagnoses in 16 families (44%), including 11 families with likely damaging variants in known genes and five families with predicted deleterious variants in disease genes (IGSF10, MND1, MRPS22, and SOHLH1) not previously associated with POI. Of the 16 families, 2 (13%) had evidence for potentially pathogenic variants at more than one locus. Absence of heterozygosity consistent with identity-by-descent mediated recessive disease burden contributes to molecular diagnosis in 15 of 16 (94%) families. GeneMatcher allowed identification of additional families from diverse genetic backgrounds. CONCLUSIONS: ES analysis of a POI cohort further characterized locus heterogeneity, reaffirmed the association of genes integral to meiotic recombination, demonstrated the likely contribution of genes involved in hypothalamic development, and documented multilocus pathogenic variation suggesting the potential for oligogenic inheritance contributing to the development of POI.
Topics
Citations
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82 citations
OpenAlex cited_by_count (cache / database)
15 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- Exome sequencing of a primary ovarian insufficiency cohort reveals common molecular etiologies for a spectrum of disease 2019
- Exome Sequencing of a Primary Ovarian Insufficiency Cohort Reveals Common Molecular Etiologies for a Spectrum of Disease 2019
- Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross‐sectional study 2019
- Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross‐sectional study 2019
- Clinical and Laboratory Characteristics of Hyperprolactinemia in Children and Adolescents: National Survey 2019
- Exome Sequencing of a Primary Ovarian Insufficiency Cohort Reveals Common Molecular Etiologies for a Spectrum of Disease 2019
- Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in two siblings; same mutation but different clinical manifestations at onset 2022
- Whole-exome sequencing reveals new potential genes and variants in patients with premature ovarian insufficiency 2022
- First Report of a de novo 10q23.31q23.33 Microdeletion: Obesity, Intellectual Disability and Microcephaly 2021
- Investigation of the molecular genetic causes of non-syndromic primary ovarian ınsufficiency by next generation sequencing analysis 2024