Otozomal resesif işitme kayıplı ailelerde otozigozite taraması ile MYO7A mutasyonlarının gösterilmesi
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Date
2011
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Biyoteknoloji Enstitüsü
Abstract
Hearing loss is the most common sensorial disorder. Congenital or prelingual hearing loss occurs approximately in one case per 1000 live births. Genetic causes account for 50% of cases. Additional findings are present in 30% of cases leading to the diagnosis of a syndrome . Autosomal recessive transmission occurs in 80% of hereditary deafness. To date, 38 genes in which mutations are responsible for autosomal recessive deafness have been identified. Mutations in GJB2, encoding connexin 26, are the most commonly identified cause of sensorineural hearing loss in Caucasians. Our data and the results of other studies show that the autosomal recessive inheritance accounts for more than 90% of genetic cases in Turkey. The GJB2 gene is the most common cause accounting for approximately 20% of cases.Due to the high rate of consanguineous marriages in Turkey as well as the traditional settlements in isolated small villages, rare autosomal recessive deafness alleles are frequently present in affected individuals . One of the previously identified deafness genes, MYO7A , is on the q13.5 region of chromosome 11. This gene consists of 48 coding exon, and codes a protein containing 2215 amino acids. Mutations in this gene cause Usher syndrome type 1B, atypical Usher syndrome, as well as non-syndromic recessive (DFNB2) and dominant (DFNA11) sensorineural hearing loss.This study included 55 unrelated multiplex families with sensorineural hearing loss. Autosomal recessive inheritance was evident with multiple siblings being affected as well as with the presence of parental consanguinity. The phenotypical and audiological characteristics of these families were evaluated and and no syndromic findings or environmental cause for hearing loss were detected. Mutations in GJB2 were negative in all families. Whenever genomewide SNP-based autozygozity mapping showed an autozygous segment flanking MYO7A in a family, mutation analysis was performed. The aim of this study was to reveal the spectrum of MYO7A mutations in Turkey to facilitate molecular diagnosis in clinical setting.MYO7A mutations were detected in 5 out of 7 families, where an autozygotic region demonstrated by microarrays was found to flank the gene. In the remaining two families no change has been identified in this gene.The following homozygous mutations were found in affected individuals : c.5824 G>A (p.G1924R) (one family), in c.5838delT (p.F1946LfsX24) (one family), c.6487 G>A (p.G2163S) (one family), c.5581 C>T (p.R1861X) (one family), c.5660 C>T (p.P1887L) (one family).This study shows that MYO7A mutations have a considerably high frequency in families with hearing loss in Turkey. Identifiying genes that cause hearing loss in Turkey will accelerate the molecular diagnosis and would improve accurate genetic counseling .
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Otozomal resesif, işitme kaybı