MCM8 and MCM9 Nucleotide Variants in Women With Primary Ovarian Insufficiency

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2016 Nov 2

PMID 27802094

Citations 55

Authors

Swapna Desai

Michelle Wood-Trageser

Jelena Matic

Jaqueline Chipkin

Huaiyang Jiang

Anne Bachelot

Jerome Dulon

Cinzia Sala

Caterina Barbieri

Massimiliano Cocca

Daniela Toniolo

Philippe Touraine

Selma Witchel

Aleksandar Rajkovic

Affiliations

Soon will be listed here.

Abstract

Objective: To assess the frequency of variants, including biallelic pathogenic variants, in minichromosome maintenance 8 (MCM8) and minichromosome maintenance 9 (MCM9), other genes related to MCM8-MCM9, and DNA damage repair (DDR) pathway in participants with primary ovarian insufficiency (POI).

Design: MCM8, MCM9, and genes encoding DDR proteins that have been implicated in reproductive aging were sequenced among POI participants.

Setting: Academic research institution.

Participants: All were diagnosed with POI prior to age 40 years and presented with elevated follicle-stimulating hormone levels.

Interventions: None.

Main Outcome Measures: We identified nucleotide variants in MCM8, MCM9, and genes thought to be involved in the DNA damage response pathway and/or implicated in reproductive aging.

Results: MCM8 was sequenced in 155 POI participants, whereas MCM9 was sequenced in 151 participants. Three of 155 (2%) participants carried possibly damaging heterozygous variants in MCM8, whereas 7 of 151 (5%) individuals carried possibly damaging heterozygous variants in MCM9. One participant carried a novel homozygous variant, c.1651C>T, p.Gln551*, in MCM9, which is predicted to introduce a premature stop codon in exon 9. Biallelic damaging heterozygous variants in both MCM8 and MCM9 were identified in 1 participant. Of a total of 10 participants carrying damaging heterozygous variants in either MCM8 or MCM9, 2 individuals carried heterozygous damaging variants in genes associated with either MCM8 or MCM9 or the DDR pathway.

Conclusions: We identified a significant number of potentially damaging and novel variants in MCM8 and MCM9 among participants with POI and examined multiallelic association with variants in DDR and MCM8-MCM9 interactome genes.

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