CITED2 mutations potentially cause idiopathic premature ovarian failure

Dora Janeth Fonseca, Diego Ojeda, Besma Lakhal, Rim Braham, Stefanie Eggers, Erin Turbitt, Stefan White, Sonia Grover, Garry Warne, Margaret Zacharin, Alexandra Nevin Lam, Hanène Landolsi, Hatem Elghezal, Ali Saâd, Carlos Martín Restrepo, Marc Fellous, Andrew Sinclair, Peter Koopman, Paul Laissue

Research output: Contribution to journalArticle

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Abstract

Anomalies in gonadal development in a mouse knockout model of Cited2 have been recently described. In Cited2 -/- female gonads, an ectopic cell migration was observed and the female program of sex determination was transiently delayed. We hypothesize that, in humans, this temporary inhibition of genes should be sufficient to provoke a developmental impairment of the female gonads, conducive to premature ovarian failure (POF). To establish whether CITED2 mutations are a common cause of the disease, we performed a mutational analysis of this gene in a panel of patients with POF and in a group of control women with normal fertility. We amplified and directly sequenced the complete open reading frame of CITED2 in 139 patients with POF and 290 controls. This study revealed 5 synonymous and 3 nonsynonymous variants. Among these, 7 are novel. The nonsynonymous variant c.604C>A (p.Pro202Thr) was found uniquely in 1 woman from the POF group. In silico analysis of this mutation indicated a potential deleterious effect. We conclude that mutations in CITED2 may be involved in POF pathogenesis. © 2012 Mosby, Inc. All rights reserved.
Original languageEnglish (US)
Pages (from-to)384-388
Number of pages5
JournalTranslational Research
DOIs
StatePublished - Nov 1 2012

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Primary Ovarian Insufficiency
Genes
Mutation
Gonads
Knockout Mice
Computer Simulation
Open Reading Frames
Cell Movement
Fertility
Control Groups

Cite this

Fonseca, Dora Janeth ; Ojeda, Diego ; Lakhal, Besma ; Braham, Rim ; Eggers, Stefanie ; Turbitt, Erin ; White, Stefan ; Grover, Sonia ; Warne, Garry ; Zacharin, Margaret ; Nevin Lam, Alexandra ; Landolsi, Hanène ; Elghezal, Hatem ; Saâd, Ali ; Restrepo, Carlos Martín ; Fellous, Marc ; Sinclair, Andrew ; Koopman, Peter ; Laissue, Paul. / CITED2 mutations potentially cause idiopathic premature ovarian failure. In: Translational Research. 2012 ; pp. 384-388.
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abstract = "Anomalies in gonadal development in a mouse knockout model of Cited2 have been recently described. In Cited2 -/- female gonads, an ectopic cell migration was observed and the female program of sex determination was transiently delayed. We hypothesize that, in humans, this temporary inhibition of genes should be sufficient to provoke a developmental impairment of the female gonads, conducive to premature ovarian failure (POF). To establish whether CITED2 mutations are a common cause of the disease, we performed a mutational analysis of this gene in a panel of patients with POF and in a group of control women with normal fertility. We amplified and directly sequenced the complete open reading frame of CITED2 in 139 patients with POF and 290 controls. This study revealed 5 synonymous and 3 nonsynonymous variants. Among these, 7 are novel. The nonsynonymous variant c.604C>A (p.Pro202Thr) was found uniquely in 1 woman from the POF group. In silico analysis of this mutation indicated a potential deleterious effect. We conclude that mutations in CITED2 may be involved in POF pathogenesis. {\circledC} 2012 Mosby, Inc. All rights reserved.",
author = "Fonseca, {Dora Janeth} and Diego Ojeda and Besma Lakhal and Rim Braham and Stefanie Eggers and Erin Turbitt and Stefan White and Sonia Grover and Garry Warne and Margaret Zacharin and {Nevin Lam}, Alexandra and Han{\`e}ne Landolsi and Hatem Elghezal and Ali Sa{\^a}d and Restrepo, {Carlos Mart{\'i}n} and Marc Fellous and Andrew Sinclair and Peter Koopman and Paul Laissue",
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Fonseca, DJ, Ojeda, D, Lakhal, B, Braham, R, Eggers, S, Turbitt, E, White, S, Grover, S, Warne, G, Zacharin, M, Nevin Lam, A, Landolsi, H, Elghezal, H, Saâd, A, Restrepo, CM, Fellous, M, Sinclair, A, Koopman, P & Laissue, P 2012, 'CITED2 mutations potentially cause idiopathic premature ovarian failure', Translational Research, pp. 384-388. https://doi.org/10.1016/j.trsl.2012.05.006

CITED2 mutations potentially cause idiopathic premature ovarian failure. / Fonseca, Dora Janeth; Ojeda, Diego; Lakhal, Besma; Braham, Rim; Eggers, Stefanie; Turbitt, Erin; White, Stefan; Grover, Sonia; Warne, Garry; Zacharin, Margaret; Nevin Lam, Alexandra; Landolsi, Hanène; Elghezal, Hatem; Saâd, Ali; Restrepo, Carlos Martín; Fellous, Marc; Sinclair, Andrew; Koopman, Peter; Laissue, Paul.

In: Translational Research, 01.11.2012, p. 384-388.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CITED2 mutations potentially cause idiopathic premature ovarian failure

AU - Fonseca, Dora Janeth

AU - Ojeda, Diego

AU - Lakhal, Besma

AU - Braham, Rim

AU - Eggers, Stefanie

AU - Turbitt, Erin

AU - White, Stefan

AU - Grover, Sonia

AU - Warne, Garry

AU - Zacharin, Margaret

AU - Nevin Lam, Alexandra

AU - Landolsi, Hanène

AU - Elghezal, Hatem

AU - Saâd, Ali

AU - Restrepo, Carlos Martín

AU - Fellous, Marc

AU - Sinclair, Andrew

AU - Koopman, Peter

AU - Laissue, Paul

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Anomalies in gonadal development in a mouse knockout model of Cited2 have been recently described. In Cited2 -/- female gonads, an ectopic cell migration was observed and the female program of sex determination was transiently delayed. We hypothesize that, in humans, this temporary inhibition of genes should be sufficient to provoke a developmental impairment of the female gonads, conducive to premature ovarian failure (POF). To establish whether CITED2 mutations are a common cause of the disease, we performed a mutational analysis of this gene in a panel of patients with POF and in a group of control women with normal fertility. We amplified and directly sequenced the complete open reading frame of CITED2 in 139 patients with POF and 290 controls. This study revealed 5 synonymous and 3 nonsynonymous variants. Among these, 7 are novel. The nonsynonymous variant c.604C>A (p.Pro202Thr) was found uniquely in 1 woman from the POF group. In silico analysis of this mutation indicated a potential deleterious effect. We conclude that mutations in CITED2 may be involved in POF pathogenesis. © 2012 Mosby, Inc. All rights reserved.

AB - Anomalies in gonadal development in a mouse knockout model of Cited2 have been recently described. In Cited2 -/- female gonads, an ectopic cell migration was observed and the female program of sex determination was transiently delayed. We hypothesize that, in humans, this temporary inhibition of genes should be sufficient to provoke a developmental impairment of the female gonads, conducive to premature ovarian failure (POF). To establish whether CITED2 mutations are a common cause of the disease, we performed a mutational analysis of this gene in a panel of patients with POF and in a group of control women with normal fertility. We amplified and directly sequenced the complete open reading frame of CITED2 in 139 patients with POF and 290 controls. This study revealed 5 synonymous and 3 nonsynonymous variants. Among these, 7 are novel. The nonsynonymous variant c.604C>A (p.Pro202Thr) was found uniquely in 1 woman from the POF group. In silico analysis of this mutation indicated a potential deleterious effect. We conclude that mutations in CITED2 may be involved in POF pathogenesis. © 2012 Mosby, Inc. All rights reserved.

U2 - 10.1016/j.trsl.2012.05.006

DO - 10.1016/j.trsl.2012.05.006

M3 - Article

SP - 384

EP - 388

JO - Translational Research

JF - Translational Research

SN - 1931-5244

ER -