Top, Affected members were heterozygous for a G→A transition in exon 12 at position 1325 of the MYO6 cDNA. Bottom, Restriction enzyme analysis with HpaI mutagenesis primers (IdirA forward primer 5′-TTAGGTGCACTCTGTGGCAT-3′ and 9* (corresponding to fragment 9 of the gene) reverse mutagenesis primer 5′-GGATGATGTTTCAAAAGGTTAA-3′) identifies the G→A mutation in DFNA22 affected individuals. M = mutant; N = normal; ND = not digested.

An MYO6 mutation in affected members of an Italian kindred. Top, Pedigree of four generations of the Italian family, showing haplotypes of chromosome 6q13 markers (D6S257, D6S402, D6S681, D6S640, and DS445) and linkage to this region (yellow) in deaf individuals. Individuals with hearing loss are indicated by blackened symbols; unaffected individuals are indicated by open symbols. Bottom, Pure-tone audiograms, for right and left ears, of five affected family members. Note variability in severity of hearing loss (moderate to profound) among siblings.

The C442Y missense mutation. Top, Alignment of a portion of myosin VI from various species. Bottom, A ribbon representation of a three-dimensional model of the myosin VI motor domain. Inset, the model of myosin VI (blue) and the experimentally determined structure of chicken pectoralis myosin II (gold), which was used as template. Also shown are C442 (yellow), α-helixes (red), and β-sheets (turquoise). The model was built using the automatic homology modeling facility, Swiss Model, and the three-dimensional structures of several myosins, including the Dictyostelium discoideum myosin S1 and chicken pectoralis myosin II motor domain. The figure was created using INSIGHT and WebLabViewerLite, version 3.10 (MSI).