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. 2001 Sep;69(3):635-40.
doi: 10.1086/323156. Epub 2001 Jul 20.

MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss

S Melchionda  1 , N Ahituv, L Bisceglia, T Sobe, F Glaser, R Rabionet, M L Arbones, A Notarangelo, E Di Iorio, M Carella, L Zelante, X Estivill, K B Avraham, P Gasparini
Affiliations

MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss

S Melchionda et al. Am J Hum Genet. 2001 Sep.

Abstract

Mutations in the unconventional myosin VI gene, Myo6, are associated with deafness and vestibular dysfunction in the Snell's waltzer (sv) mouse. The corresponding human gene, MYO6, is located on chromosome 6q13. We describe the mapping of a new deafness locus, DFNA22, on chromosome 6q13 in a family affected by a nonsyndromic dominant form of deafness (NSAD), and the subsequent identification of a missense mutation in the MYO6 gene in all members of the family with hearing loss.

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Figures

Figure 1
Figure 1
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.
Figure 2
Figure 2
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.
Figure 3
Figure 3
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).
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References

Electronic-Database Information

    1. GenBank, http://www.ncbi.nlm.nih.gov/Genbank (for Myosin VI [MYO6; U90236])
    1. Hereditary Hearing Loss, http://dnalab-www.uia.ac.be/dnalab/hhh (for genetic information on myosins)
    1. Myosin Motor Domain Sequence Alignment, http://www.mrc-lmb.cam.ac.uk/myosin/trees/txalign.html (for structural data)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov./Omim (for myosin VIIA gene [MIM 276903], myosin VI gene [MIM 600970], myosin XV [MIM 602666], and KCNQ3 [MIM 602232])
    1. Swiss Model, http://www.expasy.ch/swissmod/SWISS-MODEL.html (for protein modeling)

References

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