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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.

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.

SUBMITTER: Okutman O

PROVIDER: S-EPMC5427651 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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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.

Okutman Ozlem O Muller Jean J Skory Valerie V Garnier Jean Marie JM Gaucherot Angeline A Baert Yoni Y Lamour Valérie V Serdarogullari Munevver M Gultomruk Meral M Röpke Albrecht A Kliesch Sabine S Herbepin Viviana V Aknin Isabelle I Benkhalifa Moncef M Teletin Marius M Bakircioglu Emre E Goossens Ellen E Charlet-Berguerand Nicolas N Bahceci Mustafa M Tüttelmann Frank F Viville STéphane S

Journal of assisted reproduction and genetics 20170411 5

<h4>Purpose</h4>The purpose of this study was to identify mutations that cause non-syndromic male infertility using whole exome sequencing of family cases.<h4>Methods</h4>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 S ...[more]

PMID: 28401488

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Project description:BACKGROUND:During spermatogenesis, the H2B family, member W (H2B.W) gene, en- codes a testis specific histone that is co-localized with telomeric sequences and has the potential role to mediate the sperm-specific chromatin remodeling. Previously H2B.W genetic variants were reported to be involved in susceptibility to spermatogenesis im- pairment. In the present study, two single nucleotide polymorphisms (SNPs) in 5?UTR and exon 1 of H2B.W gene were examined to investigate possible association of these polymorphisms with male infertility in Iranian population. MATERIALS AND METHODS:This case control study was conducted in Royan institute during four-year period (2010-2013). Genetic alteration of two SNPs loci, -9C>T and 368A>G, in H2B.W gene were indicated in 92 infertile men who were divided into two main groups includ- ing azoospermia (n=46) and sever oligozoospermia (n=46), while there was 60 fertile men as control group. Azoosperima was also divided into three sub-groups including sertoli cell only syndrome (SCOS, n=21), complete maturation arrest (CMA, n=17) and hypo spermatogenesis (n=8) according to testicular biopsy. For analysis, polymerase chain reaction-restriction frag- ment length polymorphism (PCR-RFLP) technique was applied. RESULTS:The frequency of allele -9T was significantly higher in CMA group than in patients with SCOS (P<0.05). The haplotype TA (corresponding to simultaneous occur- rence of -9T and 368A) compared with haplotype CA (corresponding to simultaneous occurrence of -9C and 368A) in patients suffering from CMA significantly increased, compared with patients had SCOS (P<0.05). However, statistical studies indicated that in general, the distribution frequencies of -9C>T and 368A>G had no significant difference between the infertile groups and control (P=0.859 and P=0.812, respectively). CONCLUSION:This investigation showed that SNP -9C>T might be contribute to CMA in azoo- spermic patients and SNP 368A>G had no correlation with male infertility in Iranian population.

Dataset Information

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

Publications

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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