Hearing loss segregating in family PKDF468 is associated with a missense ELMOD3 allele.

<p>(A) Pedigree of the family in which the <i>DFNB88</i> locus was mapped. The filled symbols represent affected individuals, and a double horizontal line connecting parents represents a consanguineous marriage. The alleles forming the risk haplotypes are boxed. The short tandem repeat (STR) markers, their relative map positions (Mb) according to UCSC Genome Bioinformatics Build GRCh37 (hg19), and their genetic positions (cM) based on the Marshfield genetic map are shown next to the pedigree. Haplotype analysis revealed a linkage region of 4.3 cM (0.91 Mb) that was delimited by proximal meiotic recombination in individual V:6 (arrowhead) at marker <i>D2S1387</i> (103.16 cM; arrow) and distal recombination at marker <i>D2S2232</i> (107.46 cM; arrow) in individual V:11 (arrowhead). (B) Pure-tone audiograms for family PKDF468 V:2 (25-year-old female) and V:5 (20-year-old male). The symbols ‘o’ and ‘x’ denote air conduction pure-tone thresholds, and the ‘<’ and ‘>’ symbols denote bone conduction thresholds in the right and the left ears, respectively. (C) The linkage interval that defines the <i>DFNB88</i> locus for family PKDF468 partially overlaps with <i>DFNA43</i>. The relative locations and orientations of the genes and mRNAs are indicated with arrows. Individual V:2 DNA sample was used for exome sequencing, while individuals V:5 and V:11 samples were used for Sanger sequencing of coding, non-coding, and flanking sequences of the exon-intron boundaries of the known candidate genes in <i>DFNB88</i> linkage interval.