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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Orphanet Journal of Rare Diseases 1/2014

EPS8, encoding an actin-binding protein of cochlear hair cell stereocilia, is a new causal gene for autosomal recessive profound deafness

Zeitschrift:
Orphanet Journal of Rare Diseases > Ausgabe 1/2014
Autoren:
Asma Behlouli, Crystel Bonnet, Samia Abdi, Aïcha Bouaita, Andrea Lelli, Jean-Pierre Hardelin, Cataldo Schietroma, Yahia Rous, Malek Louha, Ahmed Cheknane, Hayet Lebdi, Kamel Boudjelida, Mohamed Makrelouf, Akila Zenati, Christine Petit
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1750-1172-9-55) contains supplementary material, which is available to authorized users.
Asma Behlouli, Crystel Bonnet, Samia Abdi contributed equally to this work.

Competing interest

The authors declare that they have no competing interests.

Abstract

Background

Almost 90% of all cases of congenital, non-syndromic, severe to profound inherited deafness display an autosomal recessive mode of transmission (DFNB forms). To date, 47 causal DFNB genes have been identified, but many others remain to be discovered. We report the study of two siblings born to consanguineous Algerian parents and affected by isolated, profound congenital deafness.

Method

Whole-exome sequencing was carried out on these patients after a failure to identify mutations in the DFNB genes frequently involved.

Results

A biallelic nonsense mutation, c.88C > T (p.Gln30*), was identified in EPS8 that encodes epidermal growth factor receptor pathway substrate 8, a 822 amino-acid protein involved in actin dynamics. This mutation predicts a truncated inactive protein or no protein at all. The mutation was also present, in the heterozygous state, in one clinically unaffected sibling and in both unaffected parents, and was absent from the other two unaffected siblings. It was not found in 120 Algerian normal hearing control individuals or in the Exome Variant Server database. EPS8 is an F-actin capping and bundling protein. Mutant mice lacking EPS8 (Eps8−/− mice), which is present in the hair bundle, the sensory antenna of the auditory sensory cells that operate the mechano-electrical transduction, are also profoundly deaf and have abnormally short hair bundle stereocilia.

Conclusion

This new DFNB form is likely to arise from abnormal hair bundles resulting in compromised detection of physiological sound pressures.
Zusatzmaterial
Additional file 1: Table S1.: Primers for PCR amplification of EPS8 exons (DOCX 16 KB)
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Authors’ original file for figure 1
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Authors’ original file for figure 2
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Literatur
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