Ammar-Khodja et al. (2009) applied a systematic approach, involving haplotyping and genotyping, to depict the molecular etiology of non-syndromic deafness in 50 families and 9 sporadic cases from Algeria. Two families with non-syndromic deafness carried novel unclassified variants of unknown pathogenic effect in the CDH23 gene.

Using targeted DNA capture and massively parallel sequencing (MPS), Brownstein et al. (2011) screened 246 genes known to be responsible for human or mouse deafness in 11 probands of Jewish and Palestinian Arab origin and identified mutations associated with hearing loss in a subset of these probands and their extended families. Among these 11 families, they analyzed nine affected members with profound hearing loss and two relatives with normal hearing from one family of Jewish-Algerian descent. Hearing loss in the family was found to be consistent with autosomal recessive inheritance. In genomic DNA from the proband, a novel variant in CDH23 was observed in 100% of reads, indicating a clear homozygosity. This variant corresponds to CDH23 c.7903G > T, p.V2635F and co-segregates perfectly with hearing loss in the extended kindred. The CDH23 mutation was also screened in hearing controls and other deaf probands of Jewish origin. A proband from another consanguineous family of Algerian origin with two affected sibs, was found to be homozygous for the mutation, which segregated with hearing loss in his family. Another deaf proband with partial Algerian ancestry was found to be heterozygous for CDH23 p.V2635F. All 68 exons of CDH23 were sequenced in genomic DNA of this proband, but no second mutation was detected. This finding led Brownstein et al. (2011) to assume that this proband may be a carrier of CDH23 p.V2635F, with his hearing loss due to another gene.

Shahin et al. (2010) carried out a molecular study to identify the genes responsible for inherited hearing loss, by using high-density SNP arrays to genotype the DNA of 155 relatives (including: 78 patients, 28 of their hearing siblings, and 49 parents) from 20 consanguineous Palestinian families with prelingual bilateral autosomal recessive non-syndromic hearing loss (NSHL). In 14 families, Shahin et al. (2010) identified the allele responsible for hearing loss by screening a single candidate gene, known to be associated with hearing loss, in the longest homozygous region. Among these 14 families, Shahin et al. (2010) identified three different missense mutations in the CDH3, the gene responsible for DFNB12, in three consanguineous Palestinian families with five (three males and two females), three (two males and one female), and four (two males and two females) affected members, respectively. Deaf individuals from each of these three families carried one of these three mutations in homozygous state. These mutations were: c.1427C>T (Pro346Ser), c.1428C>T (Pro346Leu), and c.2065C>T (Pro559Ser).

By genomewide linkage analysis followed by homozygosity mapping of a consanguineous Sunni family, living in an isolated village in Syria, affected with sensorineural hearing loss, Chaib et al. (1996) identified a candidate disease locus, designated DFNB12, to chromosome 10q21-q22 (a lod score of 6.40 was obtained with marker D10S535). Analysis of adjacent markers placed the gene distal to D10S529 and proximal to D10S532 in a 11- to 15-cM region. Chaib et al. (1996) noted that the homologous murine region for DFNB12 contains three deaf mouse mutants, including Jackson circler (jc), Waltzer (v), and Ames Waltzer (av). This finding is suggestive that each of these mouse mutants is a candidate mouse model for the DFNB12-associated hearing impairment.