EPS8, encoding an actin-binding protein of cochlear hair cell stereocilia, is a new causal gene for autosomal recessive profound deafness. - Archive ouverte HAL Access content directly
Journal Articles Orphanet Journal of Rare Diseases Year : 2014

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

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Asma Behlouli
  • Function : Author
  • PersonId : 955823
Samia Abdi
  • Function : Author
  • PersonId : 955824
Yahia Rous
  • Function : Author
  • PersonId : 955828
Malek Louha
  • Function : Author
  • PersonId : 955829
Ahmed Cheknane
  • Function : Author
  • PersonId : 955830
Hayet Lebdi
  • Function : Author
  • PersonId : 955831
Kamel Boudjelida
  • Function : Author
  • PersonId : 955832
Mohamed Makrelouf
  • Function : Author
  • PersonId : 955833
Akila Zenati
  • Function : Author
  • PersonId : 955834

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.
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inserm-00986102 , version 1 (30-04-2014)

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Asma Behlouli, Crystel Bonnet, Samia Abdi, Aïcha Bouaita, Andrea Lelli, et al.. EPS8, encoding an actin-binding protein of cochlear hair cell stereocilia, is a new causal gene for autosomal recessive profound deafness.. Orphanet Journal of Rare Diseases, 2014, 9 (1), pp.55. ⟨10.1186/1750-1172-9-55⟩. ⟨inserm-00986102⟩
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