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Article Dans Une Revue Journal of Medical Genetics Année : 2011

High incidence of recurrent copy number variants in patients with isolated and syndromic Mullerian aplasia

Serena Nik-Zainal
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Mekayla Storer
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Ni Huang
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Roland Rad
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Lionel Willatt
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Tomas Fitzgerald
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Vicki Martin
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Richard Sandford
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Nigel P Carter
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Matthew Hurles
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Résumé

Background: Congenital malformations involving the Mullerian ducts are observed in around 5% of infertile women. Complete aplasia of the uterus, cervix, and upper vagina, also termed Mullerian aplasia or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome occurs with an incidence of around 1 in 4,500 female births, and occurs in both isolated and syndromic forms. Previous reports have suggested that a proportion of cases, especially syndromic cases, are caused by variation in copy number at different genomic loci. Methods: In order to obtain an overview of the contribution of copy number variation to both isolated and syndromic forms of Mullerian aplasia, we performed copy number assays in a series of 63 cases, of which 25 were syndromic and 38 isolated. Results: We report a high incidence (9/63, 14%) of recurrent copy number variants in this cohort. These comprised four cases of microdeletion at 16p11.2, an autism susceptibility locus not previously associated with Mullerian aplasia,four cases of microdeletion at 17q12, and one case of a distal 22q11.2 microdeletion. Microdeletions at 16p11.2 and 17q12 were found in 4/38 (10.5%) cases with isolated Mullerian aplasia, and at 16p11.2, 17q12 and 22q11.2 (distal) in 5/25 cases (20%) with syndromic Mullerian aplasia. Conclusion: Our finding of microdeletion at 16p11.2 in 2/38 (5%) of isolated and 2/25 (8%) of syndromic cases suggests a significant contribution of this copy number variant alone to the pathogenesis of Mullerian aplasia. Overall, the high incidence of recurrent copy number variants in all forms of Mullerian aplasia has implications for our understanding of the aetiopathogenesis of the condition, and for genetic counseling in families affected by it.
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hal-00604038 , version 1 (28-06-2011)

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Serena Nik-Zainal, Reiner Strick, Mekayla Storer, Ni Huang, Roland Rad, et al.. High incidence of recurrent copy number variants in patients with isolated and syndromic Mullerian aplasia. Journal of Medical Genetics, 2011, 48 (3), pp.197. ⟨10.1136/jmg.2010.082412⟩. ⟨hal-00604038⟩

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