Sensorineural deafness and male infertility: a contiguous gene deletion syndrome

J Med Genet. 2007 Apr;44(4):233-40. doi: 10.1136/jmg.2006.045765. Epub 2006 Nov 10.

Abstract

Background: Syndromic hearing loss that results from contiguous gene deletions is uncommon. Deafness-infertility syndrome (DIS) is caused by large contiguous gene deletions at 15q15.3.

Methods: Three families with a novel syndrome characterised by deafness and infertility are described. These three families do not share a common ancestor and do not share identical deletions. Linkage was established by completing a genome-wide scan and candidate genes in the linked region were screened by direct sequencing.

Results: The deleted region is about 100 kb long and involves four genes (KIAA0377, CKMT1B, STRC and CATSPER2), each of which has a telomeric duplicate. This genomic architecture underlies the mechanism by which these deletions occur. CATSPER2 and STRC are expressed in the sperm and inner ear, respectively, consistent with the phenotype in persons homozygous for this deletion. A deletion of this region has been reported in one other family segregating male infertility and sensorineural deafness, although congenital dyserythropoietic anaemia type I (CDAI) was also present, presumably due to a second deletion in another genomic region.

Conclusion: We have identified three families segregating an autosomal recessive contiguous gene deletion syndrome characterised by deafness and sperm dysmotility. This new syndrome is caused by the deletion of contiguous genes at 15q15.3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Calcium Channels
  • Chromosome Breakage
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15 / genetics*
  • Chromosomes, Human, Pair 15 / ultrastructure
  • Consanguinity
  • Creatine Kinase / deficiency
  • Creatine Kinase / genetics
  • Gene Deletion*
  • Genes, Recessive
  • Haplotypes
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Infertility, Male / genetics*
  • Ion Channels / deficiency
  • Ion Channels / genetics
  • Ion Channels / physiology
  • Iran
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Pedigree
  • Phosphotransferases (Phosphate Group Acceptor)
  • Protein Tyrosine Phosphatases / genetics
  • Pseudogenes
  • Repetitive Sequences, Nucleic Acid*
  • Seminal Plasma Proteins
  • Sequence Alignment
  • Sperm Motility / genetics
  • Syndrome
  • Tandem Repeat Sequences*

Substances

  • CATSPER2 protein, human
  • Calcium Channels
  • Ion Channels
  • Membrane Proteins
  • STRC protein, human
  • Seminal Plasma Proteins
  • CKMT1A protein, human
  • Creatine Kinase
  • Phosphotransferases (Phosphate Group Acceptor)
  • PPIP5K1 protein, human
  • Protein Tyrosine Phosphatases