MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency

S Desai, M Wood-Trageser, J Matic, J Chipkin, H Jiang, A Bachelot, J Dulon, C Sala, C Barbieri, M Cocca, D Toniolo, P Touraine, S Witchel, A Rajkovic

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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 folliclestimulating hormone levels. Interventions: None. Main Outcome Measures:Weidentified nucleotide variants inMCM8, 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∗, inMCM9, 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. © 2017 by the Endocrine Society.
Original languageEnglish
Pages (from-to)576-582
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume102
Issue number2
DOIs
Publication statusPublished - 2017

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Primary Ovarian Insufficiency
Nucleotides
Maintenance
DNA Damage
DNA Repair
Repair
Genes
DNA
Aging of materials

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Desai, S., Wood-Trageser, M., Matic, J., Chipkin, J., Jiang, H., Bachelot, A., ... Rajkovic, A. (2017). MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency. Journal of Clinical Endocrinology and Metabolism, 102(2), 576-582. https://doi.org/10.1210/jc.2016-2565

MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency. / Desai, S; Wood-Trageser, M; Matic, J; Chipkin, J; Jiang, H; Bachelot, A; Dulon, J; Sala, C; Barbieri, C; Cocca, M; Toniolo, D; Touraine, P; Witchel, S; Rajkovic, A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 102, No. 2, 2017, p. 576-582.

Research output: Contribution to journalArticle

Desai, S, Wood-Trageser, M, Matic, J, Chipkin, J, Jiang, H, Bachelot, A, Dulon, J, Sala, C, Barbieri, C, Cocca, M, Toniolo, D, Touraine, P, Witchel, S & Rajkovic, A 2017, 'MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency', Journal of Clinical Endocrinology and Metabolism, vol. 102, no. 2, pp. 576-582. https://doi.org/10.1210/jc.2016-2565
Desai, S ; Wood-Trageser, M ; Matic, J ; Chipkin, J ; Jiang, H ; Bachelot, A ; Dulon, J ; Sala, C ; Barbieri, C ; Cocca, M ; Toniolo, D ; Touraine, P ; Witchel, S ; Rajkovic, A. / MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency. In: Journal of Clinical Endocrinology and Metabolism. 2017 ; Vol. 102, No. 2. pp. 576-582.
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T1 - MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency

AU - Desai, S

AU - Wood-Trageser, M

AU - Matic, J

AU - Chipkin, J

AU - Jiang, H

AU - Bachelot, A

AU - Dulon, J

AU - Sala, C

AU - Barbieri, C

AU - Cocca, M

AU - Toniolo, D

AU - Touraine, P

AU - Witchel, S

AU - Rajkovic, A

PY - 2017

Y1 - 2017

N2 - 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 folliclestimulating hormone levels. Interventions: None. Main Outcome Measures:Weidentified nucleotide variants inMCM8, 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∗, inMCM9, 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. © 2017 by the Endocrine Society.

AB - 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 folliclestimulating hormone levels. Interventions: None. Main Outcome Measures:Weidentified nucleotide variants inMCM8, 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∗, inMCM9, 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. © 2017 by the Endocrine Society.

U2 - 10.1210/jc.2016-2565

DO - 10.1210/jc.2016-2565

M3 - Article

VL - 102

SP - 576

EP - 582

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -