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Am J Hum Genet. 2016 Oct 6;99(4):942-949. doi: 10.1016/j.ajhg.2016.08.004. Epub 2016 Sep 15.

Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa Syndrome.

Author information

1
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Institute of Reproductive Genetics, Anhui Medical University, Hefei 230022, China; School of Life Science, Anhui Medical University, Hefei 230022, China. Electronic address: fxzhu@ahmu.edu.cn.
2
School of Life Science, Anhui Medical University, Hefei 230022, China.
3
Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
4
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Institute of Reproductive Genetics, Anhui Medical University, Hefei 230022, China.
5
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Institute of Reproductive Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China.
6
School of Medicine, Robinson Research Institute, The University of Adelaide, and South Australian Health and Medical Research Institute, Adelaide, South Australia 5006, Australia.
7
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Institute of Reproductive Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. Electronic address: caoyunxia6@126.com.

Abstract

Acephalic spermatozoa syndrome is a rare and severe form of teratozoospermia characterized by a predominance of headless spermatozoa in the ejaculate. Family clustering and consanguinity suggest a genetic origin; however, causative mutations have yet to be identified. We performed whole-exome sequencing in two unrelated infertile men and subsequent variant filtering identified one homozygous (c.824C>T [p.Thr275Met]) and one compound heterozygous (c.1006C>T [p.Arg356Cys] and c.485T>A [p.Met162Lys]) SUN5 (also named TSARG4) variants. Sanger sequencing of SUN5 in 15 additional unrelated infertile men revealed four compound heterozygous (c.381delA [p.Val128Serfs7] and c.824C>T [p.Thr275Met]; c.381delA [p.Val128Serfs7] and c.781G>A [p.Val261Met]; c.216G>A [p.Trp72] and c.1043A>T [p.Asn348Ile]; c.425+1G>A/c.1043A>T [p.Asn348Ile]) and two homozygous (c.851C>G [p.Ser284]; c.350G>A [p.Gly114Arg]) variants in six individuals. These 10 SUN5 variants were found in 8 of 17 unrelated men, explaining the genetic defect in 47.06% of the affected individuals in our cohort. These variants were absent in 100 fertile population-matched control individuals. SUN5 variants lead to absent, significantly reduced, or truncated SUN5, and certain variants altered SUN5 distribution in the head-tail junction of the sperm. In summary, these results demonstrate that biallelic SUN5 mutations cause male infertility due to autosomal-recessive acephalic spermatozoa syndrome.

PMID:
27640305
PMCID:
PMC5065659
DOI:
10.1016/j.ajhg.2016.08.004
[Indexed for MEDLINE]
Free PMC Article

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