Mapping of DFNB3/MYO15A in Punjabi families with non-syndromic congenital deafness

Deafness is inherited most commonly following autosomal recessive mode of inheritance as isolated clinical finding .Genetic and clinical heterogeneity of disorder prevent pooling of affected families and is a big barrier in gene mapping by conventional techniques. However, because of consanguinity, linkage analysis can be used to find disease causing loci /genes in small nuclear families. This study demonstrates the power of this technique by identifying two families segregating their disease phenotype with DFNB3/MYO15A. Introduction. Deafness is partial or total failure to hear or distinguish sounds and also distressed potential of speech in affected individuals. It is the most-wide spread neuro-sensory trouble in humans which affects 0.1% of the population worldwide and most of which are genetically inheritable [1]. Frequent consanguineous marriages in Pakistani population favors genetic characterization of hereditary disorders like deafness [2]. Identification of molecular components of genes by forward genetics is hard due to tremendous genetic as well as clinical heterogeneity. In this scenario, linkage analysis is a valuable technique not only for mapping new regions, but also to refine the boundaries of already identified loci [3, 4]. Exclusion analysis for known loci is helpful in refining the reported regions or detecting the variant alleles in families linked to the loci with already known gene. This study will help to offer genetic counseling to the families and to reduce the incidence of hereditary deafness in Pakistani population thereby decreasing socio-economic burden. Materials and Methods Families segregating non-syndromic sensorineural hearing loss were identified by an extensive search from the schools and centers for special education located in different districts of Punjab province. A total of 10 families with three or more deafness affected individuals and segregating autosomal recessive deafness were enrolled in the study and blood samples were collected from each affected individual, normal siblings, parents and grandparents, depending upon their availability and consent. DNA was extracted from the blood samples and used in the linkage analyses by genotyping three fully informative fluorescently labeled primers (D17S2207, D17S2206 and D17S2196) used for screening of MYO 15A.Haplotypes were constructed to find the pattern of inheritance among the affected and normal individuals of each family under study. If the deafness phenotype in a family showed potential linkage to DFNB3 locus (MYO15A), more closely spaced STR markers were genotyped. Two-point LOD scores (Zmax) were calculated for each family using MLINK software.