A novel nonsense mutation in MYO6 is associated with progressive nonsyndromic hearing loss in a Danish DFNA22 family.
Autosomal dominant inheritance is described in about 20% of all nonsyndromic hearing loss with currently 54 distinct loci (DFNA1-54), and >20 different genes identified. Seven different unconventional myosin genes are involved in ten different types of syndromic and nonsyndromic hearing loss with different patterns of inheritance: MYO7A in DFNA11/DFNB2/USH1B, MYH9 in DFNA17, MYH14 in DFNA4, MYO6 in DFNA22/DFNB37, MYO3A in DFNB30, MYO1A in DFNA48, and MYO15A in DFNB3. Two missense mutations in MYO6 (p.C442Y and p.H246R) have been characterized in families of Italian and American Caucasian extraction with autosomal dominant hearing loss, respectively, and the latter was associated with cardiomyopathy in some patients. Three Pakistani families had homozygosity for three MYO6 mutations (c.36insT, p.R1166X, and p.E216V, respectively), and was in one instance associated with retinal degeneration. In the present study, we linked autosomal dominant hearing loss in a large Danish family to a 38.9 Mb interval overlapping with the DFNA22/DFNB37 locus on chromosome 6q13. A novel nonsense mutation in MYO6 exon 25 (c.2545C > T; p.R849X) was identified in the family. The mutation co-segregated with the disease and the mutant allele is predicted to encode a truncated protein lacking the coiled-coil and globular tail domains. These domains are hypothesized to be essential for targeting myosin VI to its cellular compartments. No other system was involved indicating nonsyndromic loss. In conclusion, a novel nonsense MYO6 mutation causes post-lingual, slowly progressive autosomal dominant nonsyndromic moderate to severe hearing loss in a Danish family.
Sanggaard
Kirsten M
KM
Wilhelm Johannsen Centre for Functional Genome Research, Institute of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Kjaer
Klaus W
KW
Eiberg
Hans
H
Nürnberg
Gudrun
G
Nürnberg
Peter
P
Hoffman
Katrin
K
Jensen
Hanne
H
Sørum
Charlotte
C
Rendtorff
Nanna D
ND
Tranebjaerg
Lisbeth
L
D000595:Amino Acid Sequence; D001483:Base Sequence; D002896:Chromosomes, Human, Pair 6; D018389:Codon, Nonsense / Q000235:genetics*; D003718:Denmark; D005190:Family; D005799:Genes, Dominant; D008040:Genetic Linkage; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA
D018389:Codon, Nonsense; C089785:myosin VI; D018995:Myosin Heavy Chains