دورية أكاديمية
Homozygous deletion of SUN5 in three men with decapitated spermatozoa
| العنوان: | Homozygous deletion of SUN5 in three men with decapitated spermatozoa |
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| المؤلفون: | Elkhatib, Razan A., Paci, Marine, Longepied, Guy, Saias-Magnan, Jacqueline, Courbiere, Blandine, Guichaoua, Marie-Roberte, Levy, Nicolas, Metzler-Guillemain, Catherine, Mitchell, Michael J. |
| المساهمون: | Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Timone CHU - APHM (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception CHU - APHM (LA CONCEPTION), Service de Gynécologie et Obstétrique Marseille, Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement IRD : UMR237-Centre National de la Recherche Scientifique (CNRS), Département de génétique médicale Hôpital de la Timone - APHM, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Timone CHU - APHM (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Clinico-Biologique d’Assistance Médicale à la Procréation - CECOS Hôpital de la Conception - APHM |
| المصدر: | ISSN: 0964-6906. |
| بيانات النشر: | HAL CCSD Oxford University Press (OUP) |
| سنة النشر: | 2017 |
| المجموعة: | Université d'Avignon et des Pays de Vaucluse: HAL |
| مصطلحات موضوعية: | [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics |
| الوصف: | International audience ; A recent study of 17 men with decapitated spermatozoa found that 8 carried two rare SUN5 alleles, and concluded that loss of SUN5 function causes the acephalic spermatozoa syndrome. Consistent with this, the SUN5 protein localises to the head-tail junction in normal spermatozoa, and SUN proteins are known to form links between the cytoskeleton and the nucleus. However, six of the ten SUN5 variants reported were missense with an unknown effect on function, and only one man carried two high confidence loss-of-function (LOF) alleles: p.Ser284* homozygozity. One potential exonic splice mutation, homozygous variant p.Gly114Arg, was not tested experimentally. Thus, definitive proof that loss of SUN5 function causes the acephalic spermatozoa syndrome is still lacking. Based on these findings, we determined the sequence of the SUN5 gene in three related men of North African origin with decapitated spermatozoa. We found all three men to be homozygous for a deletion-insertion variant (GRCh38 - chr20:32995761_32990672delinsTGGT) that removes 5090 base pairs including exon 8 of SUN5, predicting the frameshift, p.(Leu143Serfs*30), and the inactivation of SUN5. We therefore present the second case where the acephalic spermatozoa syndrome is associated with two LOF alleles of SUN5. We also show that the p.Gly114Arg variant has a strong inhibitory effect on splicing in HeLa cells, evidence that homozygozity for p.Gly114Arg causes acephalic spermatozoa syndrome through loss of SUN5 function. Our results, together with those of the previous study, show that SUN5 is required for the formation of the sperm head-tail junction and male fertility. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-01681645; https://hal.science/hal-01681645Test; https://hal.science/hal-01681645/documentTest; https://hal.science/hal-01681645/file/Elkhatib_SUN5.pdfTest |
| DOI: | 10.1093/hmg/ddx200 |
| الإتاحة: | https://doi.org/10.1093/hmg/ddx200Test https://hal.science/hal-01681645Test https://hal.science/hal-01681645/documentTest https://hal.science/hal-01681645/file/Elkhatib_SUN5.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.4969134C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/hmg/ddx200 |
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