Molecular genetic studies in Turkish families segregating hearing loss

ABSTRACTAs more than 100 mutations have been detected in the GJB2 genewhich encodes connexin 26 protein in 69% of nonsyndromic hearingloss patients, 2 affected individuals from each of 23 families werescreened for mutations in the GJB2 gene by automated sequencing. Wedetected 2 different mutations, 35delG and delE120, in members of 8different families. 7 of the families, who did not have any mutations inthe GJB2 gene, were analyzed by a simulation program called SLINK, todetermine if they were informative enough for a genome wide linkagescan and to be used as controls. As a result of SLINK analysis, genomewide scans were carried out in the affected and unaffected individualsfrom 6 families whose estimated maximum lod scores were between 1.97and 4, and in only the affected individuals from 1 family whoseestimated maximum lod score was less than 1. From these 7 familieswho were genome wide screened using highly polymorphic microsatellitemarkers which are spaced 10 cM apart on average, 4 families whoseestimated maximum lod scores were statistically significant as a resultof SLINK, were analyzed using Linkage software to localize the diseasegene. The maximum lod score for the D17S1294 marker localized in theDFNB3 region was calculated as 3.23 in 1 of these families. As a resultof genome screening with additional markers, the maximum lod scoresfor the D17S2196 marker localized in the DFNB3 region and for theD17S2207 marker localized in the intronic sequence of the MYO15Agene in this region, were calculated as 3.48 and 3.21, respectively, inanother family. In one of these two families who were sequenced to findmutations in the MYO15A gene, a missense mutation (V2266M) wasfound in exon 33 of MYO15A. We didn?t detect linkage in the other 2families. In 2 families to whom only genome wide scan was performed,we didn?t detect any significant homozygosity in any region. In thisstudy it was shown for the first time that nonsyndromic autosomalrecessive hearing loss is associated with MYO15A in Turkish population.Key Words: Hereditary nonsyndromic hearing loss, GJB2 mutationalanalysis.4