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Analysis of two Arab families reveals additional support for a DFNB2 nonsyndromic phenotype of MYO7A

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Abstract

Variants in the head and tail domains of the MYO7A gene, encoding myosin VIIA, cause Usher syndrome type 1B (USH1B) and nonsyndromic deafness (DFNB2, DFNA11). In order to identify the genetic defect(s) underling profound deafness in two consanguineous Arab families living in UAE, we have sequenced a panel of 19 genes involved in Usher syndrome and nonsyndromic deafness in the index cases of the two families. This analysis revealed a novel homozygous insertion of AG (c.1952_1953insAG/p.C652fsX11) in exon 17 of the MYO7A gene in an Iraqi family, and a homozygous point mutation (c.5660C>T/p.P1887L) in exon 41 affecting the same gene in a large Palestinian family. Moreover, some individuals from the Palestinian family also harbored a novel heterozygous truncating variant (c.1267C>T/p.R423X) in the DFNB31 gene, which is involved in autosomal recessive nonsyndromic deafness type DFNB31 and Usher syndrome type II. Assuming an autosomal recessive mode of inheritance in the two inbred families, we conclude that the homozygous variants in the MYO7A gene are the disease-causing mutations in these families. Furthermore, given the absence of retinal disease in all affected patients examined, particularly a 28 year old patient, suggests that at least one family may segregate a DFNB2 presentation rather than USH1B. This finding further supports the premise that the MYO7A gene is responsible for two distinct diseases and gives evidence that the p.P1887L mutation in a homozygous state may be responsible for nonsyndromic hearing loss.

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Abbreviations

BERA:

Brainstem evoked response audiometry

ERG:

Electroretinograms

HL:

Hearing loss

LOD:

Linkage of disequilibirum

NMD:

Nonsense mediated decay

PTC:

Premature termination codon

PCR:

Polymerase chain reaction

RP:

Retinitis pigmentosa

VEP:

Visual evoked potential

VUS:

Variant of unknown significance

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Acknowledgments

We are indebted for the family members and patients for their participation in this research study. The laboratories of L.A. and B.R.A. are funded by the Dubai Harvard Foundation for Medical Research and the United Arab Emirates University.

Conflict of interest

All authors have declared that no competing interests exist.

Author information

Authors and Affiliations

  1. Department of Pathology, College of Medicine and Heath Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

    Salma Ben-Salem & Bassam R. Ali

  2. Partners Laboratory for Molecular Medicine, and Harvard Medical School, Boston, MA, USA

    Heidi L. Rehm

  3. GENetic DIAgnostic Network (GENDIA), Antwerp, Belgium

    Patrick J. Willems

  4. Department of Ophthalmology, Eye Specialty Hospital, Amman, Jordan

    Zakaria A. Tamimi

  5. Equipe Procédés de Criblages Moléculaires et Cellulaires, Laboratoire de micro-organismes et biomolécules, Centre de Biotechnologie de Sfax, Sfax, Tunisia

    Hammadi Ayadi

  6. Department of Paediatrics, College of Medicine and Heath Sciences, United Arab Emirates University, P.O. Box 17666, Al-Ain, United Arab Emirates

    Lihadh Al-Gazali

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  1. Salma Ben-Salem
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  2. Heidi L. Rehm
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  4. Zakaria A. Tamimi
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Correspondence to Lihadh Al-Gazali.

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Ben-Salem, S., Rehm, H.L., Willems, P.J. et al. Analysis of two Arab families reveals additional support for a DFNB2 nonsyndromic phenotype of MYO7A . Mol Biol Rep 41, 193–200 (2014). https://doi.org/10.1007/s11033-013-2851-5

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