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A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman

Authors :
Guido Alberto Gnecchi Ruscone
Mohammed Nasser Al Kindi
Marco Seri
Tania Giangregorio
Andrea Angius
Tommaso Pippucci
Paolo Gasparini
Manuela Oppo
Giorgia Girotto
Marco Sazzini
Flavia Palombo
Nadia Al-Wardy
Mazin Al Khabori
Khalsa Al Lamki
Matteo Benelli
Francesco Cucca
Alberto Magi
Giovanni Romeo
Palombo, Flavia
Al Wardy, Nadia
Ruscone, Guido Alberto Gnecchi
Oppo, Manuela
Kindi, Mohammed Nasser Al
Angius, Andrea
Al Lamki, Khalsa
Girotto, Giorgia
Giangregorio, Tania
Benelli, Matteo
Magi, Alberto
Seri, Marco
Gasparini, Paolo
Cucca, Francesco
Sazzini, Marco
Al Khabori, Mazin
Pippucci, Tommaso
Romeo, Giovanni
Al-Wardy, Nadia
Gnecchi Ruscone, Guido Alberto
Source :
Journal of human genetics. 62(2)
Publication Year :
2016

Abstract

The increased risk for autosomal recessive disorders is one of the most well-known medical implications of consanguinity. In the Sultanate of Oman, a country characterized by one of the highest rates of consanguineous marriages worldwide, prevalence of genetic hearing loss (GHL) is estimated to be 6/10 000. Families of GHL patients have higher consanguinity rates than the general Omani population, indicating a major role for recessive forms. Mutations in GJB2, the most commonly mutated GHL gene, have been sporadically described. We collected 97 DNA samples of GHL probands, affected/unaffected siblings and parents from 26 Omani consanguineous families. Analyzing a first family by whole-exome sequencing, we identified a novel homozygous frameshift duplication (c.1171_1177dupGCCATCT) in MYO15A, the gene linked to the deafness locus DFNB3. This duplication was then found in a total of 8/26 (28%) families, within a 849 kb founder haplotype. Reconstruction of haplotype structure at MYO15A surrounding genomic regions indicated that the founder haplotype branched out in the past two to three centuries from a haplotype present worldwide. The MYO15A duplication emerges as the major cause of GHL in Oman. These findings have major implications for the design of GHL diagnosis and prevention policies in Oman.

Details

ISSN :
1435232X
Volume :
62
Issue :
2
Database :
OpenAIRE
Journal :
Journal of human genetics
Accession number :
edsair.doi.dedup.....c20b582487166c73b78058776bd9fbf9