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. 2012 Feb;55(2):99-102.
doi: 10.1016/j.ejmg.2011.12.003. Epub 2011 Dec 30.

Prioritized sequencing of the second exon of MYO15A reveals a new mutation segregating in a Pakistani family with moderate to severe hearing loss

Rasheeda Bashir  1 , Amara Fatima, Sadaf Naz
Affiliations

Prioritized sequencing of the second exon of MYO15A reveals a new mutation segregating in a Pakistani family with moderate to severe hearing loss

Rasheeda Bashir et al. Eur J Med Genet. 2012 Feb.

Abstract

Mutations in MYO15A are associated with deafness in humans, and shaker 2 mice also exhibit a hearing loss due to defects of unconventional myosin 15a. We ascertained a consanguineous Pakistani family with recessively inherited moderate to severe hearing loss, which putatively segregated with markers linked to the DFNB3 locus. Prioritized sequencing of the second exon of MYO15A from the DNA of all affected individuals of family revealed a duplication of Cytosine in a stretch of seven repetitive C nucleotides (c.1185dupC). This mutation results in a frameshift and incorporates a stop codon in the open reading frame of MYO15A (p.E396fsX431). The findings of less severe hearing loss in families with linkage to DFNB3 are only reported for some individuals with mutations in exon 2 of MYO15A, which are further supported by this study. Therefore, on basis of linkage data and the presence of a less severe hearing loss phenotype, sequencing of a single exon of MYO15A can efficiently identify the causative mutations in patients from these families.

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Conflict of interest statement

Conflict of Interest: The authors declare that they have no conflict of interest

Figures

Figure 1
Figure 1. Phenotypic and genetic analysis for family HLRB3
A) Pedigree of HLRB3 along with haplotypes for markers on chromosome 17p11.2. Genetic distances of markers in cM are taken from Rutgers’ human genetic map. Affected individuals are homozygous for alleles of markers D17S2196, D17S2206 and D17S2207. The gray bar highlights the haplotype carrying the disease allele. Different sizes of alleles are denoted by letters (A, B and C). B) Audiograms for all affected family members of family HLRB3. Audiometry was conducted at two different age groups (11, 9, 7 and 14, 12, 10) for the affected children V: 3, V: 4 and V: 5 respectively. “O” indicates air conduction for right ear, while “X” indicates air conduction for left ear. Audiograms of all affected individuals in family HLRB3 revealed moderate to severe hearing loss at two different time intervals. C) A single base pair homozygous duplication of cytosine (c.1185dupC) in a stretch of seven “C” nucleotides was identified in DNA of affected individuals of family HLRB3 segregating with the phenotype. The duplication is underlined in the trace from the affected individual.
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