Homozygous deletion of SUN5 in three men with decapitated spermatozoa

Abstract : 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.
Type de document :
Article dans une revue
Human Molecular Genetics, Oxford University Press (OUP), 2017, 26 (16), pp.3167-3171. 〈10.1093/hmg/ddx200〉
Liste complète des métadonnées

https://hal.archives-ouvertes.fr/hal-01681645
Contributeur : Catherine Beaussier <>
Soumis le : lundi 16 avril 2018 - 14:29:13
Dernière modification le : lundi 27 août 2018 - 09:44:38

Fichier

Elkhatib_SUN5.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

Razan A. Elkhatib, Marine Paci, Guy Longepied, Jacqueline Saias-Magnan, Blandine Courbiere, et al.. Homozygous deletion of SUN5 in three men with decapitated spermatozoa. Human Molecular Genetics, Oxford University Press (OUP), 2017, 26 (16), pp.3167-3171. 〈10.1093/hmg/ddx200〉. 〈hal-01681645〉

Partager

Métriques

Consultations de la notice

291

Téléchargements de fichiers

39