Deafness Genes in Israel: Implications for Diagnostics in the Clinic

Abstract

ABSTRACT:The identification of the molecular basis of deafness in the last decade has made a remarkable impact on genetic counseling and diagnostics for the hearing impaired population. Since the discovery of the most prevalent form of deafness associated with mutations in the GJB2 (connexin 26) gene, many other genes have been found worldwide, with a subset of these, including unique mutations, in Israel. Here, we review the current status of deafness genes in Israel and report one known mutation in a syndromic form of deafness, Usher syndrome, described in the Jewish Israeli population for the first time. In the future, the identification of specific mutations may be relevant for specific types of treatment.

The Many Faces of Sensorineural Hearing Loss: One Founder and Two Novel Mutations Affecting One Family of Mixed Jewish Ancestry

“…1) included family screening for all known Iraqi founder DFNB1 and USH2A mutations and for all known Ashkenazi founder DFNB1, USH1F, and USH3 mutations (Brownstein et al, 2009), and yielded only the obligatory heterozygous states for the Iraqi USH2A mutation ( Fig. 1 and Table 1).…”

“…Both DFNB1 and USH are recessively inherited and the numerous population-specific causative mutations identified in the respective genes make up the essence of prenatal SNHL prevention programs to date (Smith et al, 2005). The same is true for the various Jewish communities in which different founder mutations have been identified (Brownstein et al, 2009). We report the resolution of a complex case of a family of mixed Ashkenazi and Iraqi Jewish ancestry during pregnancy, illustrating the scope of clinical and molecular workup of SNHL in the genomic era.…”

“…Known founder mutations were screened as 1 previously summarized (Brownstein et al, 2009). For Sanger sequencing of the GJB2, USH2A, and SMPX genes, DNA was amplified to obtain all coding exons and their flanking regions using conventional PCR techniques.…”

Novel myosin mutations for hereditary hearing loss revealed by targeted genomic capture and massively parallel sequencing

“…All subjects were tested for GJB2 23 by Sanger sequencing. The remaining 12 deafness genes found in Jewish populations have a low prevalence, and thus known mutations were screened only in cases where subjects manifested a relevant phenotype or belonged to a relevant ethnic background.…”

“…These genes include GJB6, PCDH15, USH1C, MYO3A, SLC26A4, LOXHD1, CDH23, MYO15A, WFS1, TECTA, POU4F3 and the inverted duplication of TJP2. 3,[23][24][25] All known deafness-causing mutations in the Palestinian population were excluded, including mutations in CDH23, MYO7A, MYO15A, OTOF, PJVK, SLC26A4, TECTA, TMHS, TMPRSS3, OTOA, PTPRQ and GPSM2. 22,26,27 Massive parallel sequencing Capture libraries were created and MPS was performed, followed by bioinformatics analysis, as previously described.…”