EPS8L2 is a new causal gene for childhood onset autosomal recessive progressive hearing loss

Orphanet J Rare Dis. 2015 Aug 19:10:96. doi: 10.1186/s13023-015-0316-8.


Background: More than 70 % of the cases of congenital deafness are of genetic origin, of which approximately 80 % are non-syndromic and show autosomal recessive transmission (DFNB forms). To date, 60 DFNB genes have been identified, most of which cause congenital, severe to profound deafness, whereas a few cause delayed progressive deafness in childhood. We report the study of two Algerian siblings born to consanguineous parents, and affected by progressive hearing loss.

Method: After exclusion of GJB2 (the gene most frequently involved in non-syndromic deafness in Mediterranean countries), we performed whole-exome sequencing in one sibling.

Results: A frame-shift variant (c.1014delC; p.Ser339Alafs*15) was identified in EPS8L2, encoding Epidermal growth factor receptor Pathway Substrate 8 L2, a protein of hair cells' stereocilia previously implicated in progressive deafness in the mouse. This variant predicts a truncated, inactive protein, or no protein at all owing to nonsense-mediated mRNA decay. It was detected at the homozygous state in the two clinically affected siblings, and at the heterozygous state in the unaffected parents and one unaffected sibling, whereas it was never found in a control population of 150 Algerians with normal hearing or in the Exome Variant Server database.

Conclusion: Whole-exome sequencing allowed us to identify a new gene responsible for childhood progressive hearing loss transmitted on the autosomal recessive mode.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Connexin 26
  • Connexins
  • Consanguinity
  • Disease Progression
  • Female
  • Frameshift Mutation
  • Genes, Recessive*
  • Hearing Loss / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Microfilament Proteins
  • Pedigree


  • Connexins
  • EPS8L2 protein, human
  • GJB2 protein, human
  • Membrane Proteins
  • Microfilament Proteins
  • Connexin 26