2. Academic Validation
  3. EPS8L2 is a new causal gene for childhood onset autosomal recessive progressive hearing loss

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.
Malika Dahmani 1,  Fatima Ammar-Khodja 2,  Crystel Bonnet 3 4 5,  Gaelle M Lefèvre 6 7 8,  Jean-Pierre Hardelin 9 10 11,  Hassina Ibrahim 12,  Zahia Mallek 13,  Christine Petit 14 15 16 17 18
Affiliations

Affiliations

  • 1 Equipe de Génétique, Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène (USTHB), El Alia, Bab-Ezzouar, Algiers, Algeria. [email protected].
  • 2 Equipe de Génétique, Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène (USTHB), El Alia, Bab-Ezzouar, Algiers, Algeria. [email protected].
  • 3 Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012, Paris, France. [email protected].
  • 4 UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France. [email protected].
  • 5 Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05, France. [email protected].
  • 6 Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012, Paris, France. [email protected].
  • 7 UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France. [email protected].
  • 8 Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05, France. [email protected].
  • 9 UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France. [email protected].
  • 10 Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05, France. [email protected].
  • 11 Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75015, Paris, France. [email protected].
  • 12 Service d'otorhinolaryngologie, Centre Hospitalier Universitaire Mustapha Pacha, Algiers, Algeria. [email protected].
  • 13 Service d'otorhinolaryngologie, Centre Hospitalier Universitaire Bab El Oued, Algiers, Algeria. [email protected].
  • 14 Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012, Paris, France. [email protected].
  • 15 UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France. [email protected].
  • 16 Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05, France. [email protected].
  • 17 Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75015, Paris, France. [email protected].
  • 18 Collège de France, 75005, Paris, France. [email protected].
PMID: 26282398 DOI: 10.1186/s13023-015-0316-8
Abstract

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.

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