An exome-wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes.
human genetics
infertility
primary ovarian insufficiency
reproduction
whole exome sequencing
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
25
05
2020
revised:
16
06
2020
accepted:
25
06
2020
pubmed:
3
7
2020
medline:
13
7
2021
entrez:
3
7
2020
Statut:
ppublish
Résumé
Primary ovarian insufficiency (POI) implies the cessation of menstruation for several months in women before the age of 40 years and is a major cause of infertility. The study of the contribution of genetic factors to POI has been fueled by the use of whole exome sequencing (WES). Here, to uncover novel causative pathogenic variants and risk alleles, WES has been performed in 12 patients with familial POI (eight unrelated index cases and two pairs of sisters) and six women with early menopause and family history of POI (four index cases and one pair of sisters). Likely causative variants in NR5A1 and MCM9 genes were identified as well as a variant in INHA that requires further investigation. Moreover, we have identified more than one candidate variant in 3 out of 15 familial cases. Taken together, our results highlight the genetic heterogeneity of POI and early menopause and support the hypothesis of an oligogenic inheritance of such conditions, in addition to monogenic inheritance.
Substances chimiques
NR5A1 protein, human
0
Steroidogenic Factor 1
0
inhibin-alpha subunit
0
Inhibins
57285-09-3
MCM9 protein, human
EC 3.6.4.12
Minichromosome Maintenance Proteins
EC 3.6.4.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
293-298Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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