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Journal of Assisted Reproduction and Genetics

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11.04.2017 | Genetics

A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family

verfasst von: Ozlem Okutman, Jean Muller, Valerie Skory, Jean Marie Garnier, Angeline Gaucherot, Yoni Baert, Valérie Lamour, Munevver Serdarogullari, Meral Gultomruk, Albrecht Röpke, Sabine Kliesch, Viviana Herbepin, Isabelle Aknin, Moncef Benkhalifa, Marius Teletin, Emre Bakircioglu, Ellen Goossens, Nicolas Charlet-Berguerand, Mustafa Bahceci, Frank Tüttelmann, STéphane Viville

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 5/2017

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Abstract

Purpose

The purpose of this study was to identify mutations that cause non-syndromic male infertility using whole exome sequencing of family cases.

Methods

We recruited a consanguineous Turkish family comprising nine siblings with male triplets; two of the triplets were infertile as well as one younger infertile brother. Whole exome sequencing (WES) performed on two azoospermic brothers identified a mutation in the melanoma antigen family B4 (MAGEB4) gene which was confirmed via Sanger sequencing and then screened for on control groups and unrelated infertile subjects. The effect of the mutation on messenger RNA (mRNA) and protein levels was tested after in vitro cell transfection. Structural features of MAGEB4 were predicted throughout the conserved MAGE domain.

Results

The novel single-base substitution (c.1041A>T) in the X-linked MAGEB4 gene was identified as a no-stop mutation. The mutation is predicted to add 24 amino acids to the C-terminus of MAGEB4. Our functional studies were unable to detect any effect either on mRNA stability, intracellular localization of the protein, or the ability to homodimerize/heterodimerize with other MAGE proteins. We thus hypothesize that these additional amino acids may affect the proper protein interactions with MAGEB4 partners.

Conclusion

The whole exome analysis of a consanguineous Turkish family revealed MAGEB4 as a possible new X-linked cause of inherited male infertility. This study provides the first clue to the physiological function of a MAGE protein.

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Titel: A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family
verfasst von: Ozlem Okutman
Jean Muller
Valerie Skory
Jean Marie Garnier
Angeline Gaucherot
Yoni Baert
Valérie Lamour
Munevver Serdarogullari
Meral Gultomruk
Albrecht Röpke
Sabine Kliesch
Viviana Herbepin
Isabelle Aknin
Moncef Benkhalifa
Marius Teletin
Emre Bakircioglu
Ellen Goossens
Nicolas Charlet-Berguerand
Mustafa Bahceci
Frank Tüttelmann
STéphane Viville
Publikationsdatum: 11.04.2017
Verlag: Springer US
Erschienen in: Journal of Assisted Reproduction and Genetics / Ausgabe 5/2017
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-017-0900-z

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A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family

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Results

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