Journal article
Mutation in TDRD9 causes non-obstructive azoospermia in infertile men
Journal of medical genetics, Vol.54(9), pp.633-639
09/2017
DOI: 10.1136/jmedgenet-2017-104514
PMID: 28536242
Abstract
BackgroundAzoospermia is diagnosed when sperm cells are completely absent in the ejaculate even after centrifugation. It is identified in approximately 1% of all men and in 10%–20% of infertile males. Non-obstructive azoospermia (NOA) is characterised by the absence of sperm due to either a Sertoli cell-only pattern, maturation arrest, hypospermatogenesis or mixed patterns. NOA is a severe form of male infertility, with limited treatment options and low fertility success rates. In the majority of patients, the cause for NOA is not known and mutations in only a few genes were shown to be causative.AimWe investigated the cause of maturation arrest in five azoospermic infertile men of a large consanguineous Bedouin family.Methods and resultsUsing whole genome genotyping and exome sequencing we identified a 4 bp deletion frameshift mutation in TDRD9 as the causative mutation with a Lod Score of 3.42. We demonstrate that the mutation results in a frameshift as well as exon skipping. Immunofluorescent staining with anti-TDRD9 antibody directed towards the N terminus demonstrated the presence of the protein in testicular biopsies of patients with an intracellular distribution comparable to a control biopsy. The mutation does not cause female infertility.ConclusionThis is the first report of a recessive deleterious mutation in TDRD9 in humans. The clinical phenotype recapitulates that observed in the Tdrd9 knockout mice where this gene was demonstrated to participate in long interspersed element-1 retrotransposon silencing. If this function is preserved in human, our data underscore the importance of maintaining DNA stability in the human male germ line.
Details
- Title: Subtitle
- Mutation in TDRD9 causes non-obstructive azoospermia in infertile men
- Creators
- Maram Arafat - The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, IsraelIris Har-Vardi - Fertility and IVF Unit, Department of Obstetrics and Gynecology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelAvi Harlev - Fertility and IVF Unit, Department of Obstetrics and Gynecology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelEliahu Levitas - The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelAtif Zeadna - The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelMaram Abofoul-Azab - The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelVictor Dyomin - Institute of Pathology, Soroka University Medical Center, Beer-Sheva, IsraelVal C Sheffield - Department of Pediatrics, Division of Medical Genetics, University of Iowa, Iowa City, USAEitan Lunenfeld - The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelMahmoud Huleihel - The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelRuti Parvari - The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- Resource Type
- Journal article
- Publication Details
- Journal of medical genetics, Vol.54(9), pp.633-639
- DOI
- 10.1136/jmedgenet-2017-104514
- PMID
- 28536242
- NLM abbreviation
- J Med Genet
- ISSN
- 0022-2593
- eISSN
- 1468-6244
- Grant note
- name: The Natural Science Foundation of China (NSFC) - Israel Science Foundation (ISF) (NSFC-ISF); name: Ben Gurion University of the Negev, Faculty of Health Sciences.
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065400102771
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