PMID: identifiant
de la référence Pubmed : |
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 (21733974)  |
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| titre : |
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A new AURKC mutation causing macrozoospermia: implications for human spermatogenesis and clinical diagnosis. |
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| auteur(s) : |
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Mariem Ben Khelifa1, 2, 3, Raoudha Zouari4, Radu Harbuz1, 2, Lazhar Halouani4, Christophe Arnoult1, Joël Lunardi2, 5, Pierre Ray ( ) 1, 2, 6 |
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| laboratoire : |
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| Équipe de recherche : |
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INSERM U836, équipe 4, Muscles et pathologies |
| titre abrégé : |
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A NEW AURKC MUTATION CAUSING MACROZOOSPERMIA |
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| résumé : |
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The presence of close to 100% large-headed multi-tailed spermatozoa in the ejaculate has been described as a rare phenotype of male infertility with a very poor prognosis. We demonstrated previously that most cases were caused by a homozygous mutation (c.144delC) in the Aurora Kinase C gene (AURKC) leading to the absence or the production of a non-functional protein. AURKC deficiency in these patients blocked meiosis and resulted in the production of tetraploid spermatozoa unsuitable for fertilization. We describe here the study of two brothers presenting with large-headed spermatozoa. Molecular analysis of the AURKC gene was carried out in two brothers presenting with a typical large-headed spermatozoa phenotype. Both affected brothers were heterozygous for the c.144delC mutation. After complete sequencing of the gene a new heterozygous variant, c.436-2A>G, was identified in both patients. This mutation is located in the acceptor consensus splice site of exon 5. AURKC transcripts were extracted from one of the patient's leukocytes and reverse transcription polymerase chain reaction could be realized showing the presence of a truncated transcript indicating that c.436-2A>G leads to the skipping of exon 5. These results indicate that AURKC molecular analysis of patients with large-headed spermatozoa should not be stopped in the absence of a homozygous recurrent mutation on exon 3 but complete sequence analysis should be performed. This diagnosis is important as the identification of AURKC mutations in patients indicates that all spermatozoa will be chromosomally abnormal and that ICSI should not be attempted. |
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| domaine : |
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Sciences du Vivant/Génétique
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1360-9947 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1093/molehr/gar050 |
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| journal : |
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| Molecular Human Reproduction (Mol Hum Reprod) |
| Publisher |
Oxford University Press (OUP): Policy B1 |
| ISSN |
1360-9947 (eISSN : 1460-2407) |
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| Audience : |
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internationale |
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| date de publication : |
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12/2011 |
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date de publication
électronique : |
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06/07/2011 |
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| volume : |
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17 |
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| numéro : |
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12 |
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| page, identifiant, ... : |
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762-8 |
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| Descripteur(s) MeSH : |
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Base Sequence – DNA Mutational Analysis – Exons – Heterozygote – Humans – Infertility – Male – Meiosis – Molecular Sequence Data – Mutation – Pedigree – Polymerase Chain Reaction – Protein-Serine-Threonine Kinases – Siblings – Spermatogenesis – Spermatozoa – Tunisia |
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| contrat, financement : |
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This work is part of the project "Identification and Characterization of Genes Involved in Infertility (ICG2I)" funded by the program GENOPAT 2009 from the French Research Agency (ANR). This work was also funded in part by program CIBLE 2009 from the Rhône- Alpes Région. |
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