Suzanne de Bruijn

249 Exploring the missing heritability in subjects with hearing loss and EVA most if not all of the six M1 cases carry the CEVA haplotype in trans with the SLC26A4 variants because it seems highly unlikely that the SLC26A4 variants all have occurred on an allele with a frequency of <3% in the population. 22 Furthermore, the co-occurrence of two partial CEVA haplotypes that together exactly mimic a heterozygous CEVA haplotype in 6 of 16 individuals is highly unlikely as the frequencies of partial CEVA haplotypes in the European population are all (far) below 1%. 22 The same holds true for the two M0/CEVA cases for whom we could not determine the phase of the 12 SNPs in the CEVA haplotype. In two cases, the V1-CEVA haplotype was identified. This smaller CEVA haplotype was also reported previously in a single M1 case by Chattaraj and coworkers and likely refines the CEVA haplotype. Alternatively, the V1-CEVA haplotype harbors a different genetic defect. The shared VNTR marker alleles of the V1-CEVA and the CEVA haplotype suggest that V1-CEVA refines the boundaries of the shared genomic region to 0.57 Mb.