Human Male Infertility Caused by Mutations in the CATSPER1 Channel Protein

Matthew R Avenarius; Michael S Hildebrand; Yuzhou Zhang; Nicole C Meyer; Luke L.H Smith; Kimia Kahrizi; Hossein Najmabadi; Richard J.H Smith

doi:10.1016/j.ajhg.2009.03.004

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Human Male Infertility Caused by Mutations in the CATSPER1 Channel Protein

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Human Male Infertility Caused by Mutations in the CATSPER1 Channel Protein

Matthew R Avenarius, Michael S Hildebrand, Yuzhou Zhang, Nicole C Meyer, Luke L.H Smith, Kimia Kahrizi, Hossein Najmabadi and Richard J.H Smith

American journal of human genetics, Vol.84(4), pp.505-510

04/10/2009

DOI: 10.1016/j.ajhg.2009.03.004

PMCID: PMC2667975

PMID: 19344877

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Abstract

Male infertility, a common barrier that prevents successful conception, is a reproductive difficulty affecting 15% of couples. Heritable forms of nonsyndromic male infertility can arise from single-gene defects as well as chromosomal abnormalities. Although no CATSPER gene has been identified as causative for human male infertility, male mice deficient for members of the CatSper gene family are infertile. In this study, we used routine semen analysis to identify two consanguineous Iranian families segregating autosomal-recessive male infertility. Autozygosity by descent was demonstrated in both families for a ∼11 cM region on chromosome 11q13.1, flanked by markers D11S1765 and D11S4139. This region contains the human CATSPER1 gene. Denaturing high-performance liquid chromatography (DHPLC) and bidirectional sequence analysis of CATSPER1 in affected family members revealed two separate insertion mutations (c.539-540insT and c.948-949insATGGC) that are predicted to lead to frameshifts and premature stop codons (p.Lys180LysfsX8 and p.Asp317MetfsX18). CATSPER1 is one of four members of the sperm-specific CATSPER voltage-gated calcium channel family known to be essential for normal male fertility in mice. These results suggest that CATSPER1 is also essential for normal male fertility in humans.

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Title: Subtitle: Human Male Infertility Caused by Mutations in the CATSPER1 Channel Protein
Creators: Matthew R Avenarius - Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI 48109-0618, USA
Michael S Hildebrand - Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
Yuzhou Zhang - Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
Nicole C Meyer - Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
Luke L.H Smith - Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
Kimia Kahrizi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Evin, Tehran 19834, Iran
Hossein Najmabadi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Evin, Tehran 19834, Iran
Richard J.H Smith - Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: American journal of human genetics, Vol.84(4), pp.505-510
DOI: 10.1016/j.ajhg.2009.03.004
PMID: 19344877
PMCID: PMC2667975
NLM abbreviation: Am J Hum Genet
ISSN: 0002-9297
eISSN: 1537-6605
Publisher: Elsevier
Language: English
Date published: 04/10/2009
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006422402771

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