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A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman
- 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.
- Subjects :
- 0301 basic medicine
Proband
Adult
MYO15A
Genetics
Genetics (clinical)
Adolescent
Oman
GHL
Population
Locus (genetics)
H3M2
Consanguinity
Biology
Deafness
Myosins
Frameshift mutation
03 medical and health sciences
Young Adult
Genetic
Gene Duplication
Exome Sequencing
Gene duplication
Humans
Exome
Deafne
education
Frameshift Mutation
education.field_of_study
Base Sequence
Haplotype
Sequence Analysis, DNA
Middle Aged
Founder Effect
030104 developmental biology
Evolutionary biology
Subjects
Details
- ISSN :
- 1435232X
- Volume :
- 62
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of human genetics
- Accession number :
- edsair.doi.dedup.....c20b582487166c73b78058776bd9fbf9