Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1).
We previously linked Laing-type early-onset autosomal dominant distal myopathy (MPD1) to a 22-cM region of chromosome 14. One candidate gene in the region, MYH7, which is mutated in cardiomyopathy and myosin storage myopathy, codes for the myosin heavy chain of type I skeletal muscle fibers and cardiac ventricles. We have identified five novel heterozygous mutations--Arg1500Pro, Lys1617del, Ala1663Pro, Leu1706Pro, and Lys1729del in exons 32, 34, 35, and 36 of MYH7--in six families with early-onset distal myopathy. All five mutations are predicted, by in silico analysis, to locally disrupt the ability of the myosin tail to form the coiled coil, which is its normal structure. These findings demonstrate that heterozygous mutations toward the 3' end of MYH7 cause Laing-type early-onset distal myopathy. MYH7 is the fourth distal-myopathy gene to have been identified.
Centre for Human Genetics, Edith Cowan University, Perth, Australia.
Christopher
C
Meredith
Ralf
R
Herrmann
Cheryl
C
Parry
Khema
K
Liyanage
Danielle E
DE
Dye
Hayley J
HJ
Durling
Rachael M
RM
Duff
Kaye
K
Beckman
Marianne
M
de Visser
Maaike M
MM
van der Graaff
Peter
P
Hedera
John K
JK
Fink
Elizabeth M
EM
Petty
Phillipa
P
Lamont
Vicki
V
Fabian
Leslie
L
Bridges
Thomas
T
Voit
Frank L
FL
Mastaglia
Nigel G
NG
Laing
D002648:Child; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D049310:Distal Myopathies / Q000235:genetics* / Q000473:pathology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D018995:Myosin Heavy Chains