Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin.
Autosomal recessive limb-girdle muscular dystrophies (AR LGMDs) are a genetically heterogeneous group of disorders that affect mainly the proximal musculature. There are eight genetically distinct forms of AR LGMD, LGMD 2A-H (refs 2-10), and the genetic lesions underlying these forms, except for LGMD 2G and 2H, have been identified. LGMD 2A and LGMD 2B are caused by mutations in the genes encoding calpain 3 (ref. 11) and dysferlin, respectively, and are usually associated with a mild phenotype. Mutations in the genes encoding gamma-(ref. 14), alpha-(ref. 5), beta-(refs 6,7) and delta (ref. 15)-sarcoglycans are responsible for LGMD 2C to 2F, respectively. Sarcoglycans, together with sarcospan, dystroglycans, syntrophins and dystrobrevin, constitute the dystrophin-glycoprotein complex (DGC). Patients with LGMD 2C-F predominantly have a severe clinical course. The LGMD 2G locus maps to a 3-cM interval in 17q11-12 in two Brazilian families with a relatively mild form of AR LGMD (ref. 9). To positionally clone the LGMD 2G gene, we constructed a physical map of the 17q11-12 region and refined its localization to an interval of 1.2 Mb. The gene encoding telethonin, a sarcomeric protein, lies within this candidate region. We have found that mutations in the telethonin gene cause LGMD 2G, identifying a new molecular mechanism for AR LGMD.
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[1] Centro de Estudos do Genoma Humano, Universidade de São Paulo, São Paulo, Brazil.
Wiltshire
T J
TJ
Faulkner
G
G
Nilforoushan
A
A
Vainzof
M
M
Suzuki
O T
OT
Valle
G
G
Reeves
R
R
Zatz
M
M
Passos-Bueno
M R
MR
Jenne
D E
DE
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D064211:Connectin; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D005819:Genetic Markers; D006801:Humans; D007438:Introns; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics*; D009136:Muscular Dystrophies / Q000145:classification / Q000235:genetics*; D009679:Nuclear Family; D010375:Pedigree; D011401:Promoter Regions, Genetic; D012518:Sarcomeres / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D064211:Connectin; D005819:Genetic Markers; D009124:Muscle Proteins; C577292:TCAP protein, human