Format

Send to

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

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

Dahmani M1, Ammar-Khodja F2, Bonnet C3,4,5, Lefèvre GM6,7,8, Hardelin JP9,10,11, Ibrahim H12, Mallek Z13, Petit C14,15,16,17,18.

Author information

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. malikadahmani.usthb@gmail.com.
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. fatima.khodja@gmail.com.
3
Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012, Paris, France. crystel.bonnet@inserm.fr.
4
UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France. crystel.bonnet@inserm.fr.
5
Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05, France. crystel.bonnet@inserm.fr.
6
Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012, Paris, France. gaelle.lefevre@inserm.fr.
7
UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France. gaelle.lefevre@inserm.fr.
8
Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05, France. gaelle.lefevre@inserm.fr.
9
UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France. jean-pierre.hardelin@pasteur.fr.
10
Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05, France. jean-pierre.hardelin@pasteur.fr.
11
Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75015, Paris, France. jean-pierre.hardelin@pasteur.fr.
12
Service d'otorhinolaryngologie, Centre Hospitalier Universitaire Mustapha Pacha, Algiers, Algeria. ibrahim.hassina@yahoo.fr.
13
Service d'otorhinolaryngologie, Centre Hospitalier Universitaire Bab El Oued, Algiers, Algeria. kacizahra@yahoo.fr.
14
Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012, Paris, France. christine.petit@pasteur.fr.
15
UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France. christine.petit@pasteur.fr.
16
Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05, France. christine.petit@pasteur.fr.
17
Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75015, Paris, France. christine.petit@pasteur.fr.
18
Collège de France, 75005, Paris, France. christine.petit@pasteur.fr.

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.

PMID:
26282398
PMCID:
PMC4539681
DOI:
10.1186/s13023-015-0316-8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center