Limb-girdle muscular dystrophy in the United States.
Limb-girdle muscular dystrophy (LGMD) has been linked to 15 chromosomal loci, 7 autosomal-dominant (LGMD1A to E) and 10 autosomal-recessive (LGMD2A to J). To determine the distribution of subtypes among patients in the United States, 6 medical centers evaluated patients with a referral diagnosis of LGMD. Muscle biopsies provided histopathology and immunodiagnostic testing, and their protein abnormalities along with clinical parameters directed mutation screening. The diagnosis in 23 patients was a disorder other than LGMD. Of the remaining 289 unrelated patients, 266 had muscle biopsies sufficient for complete microscopic evaluation; 121 also underwent Western blotting. From this combined evaluation, the distribution of immunophenotypes is 12% calpainopathy, 18% dysferlinopathy, 15% sarcoglycanopathy, 15% dystroglycanopathy, and 1.5% caveolinopathy. Genotypes distributed among 2 dominant and 7 recessive subtypes have been determined for 83 patients. This study of a large racially and ethnically diverse population of patients with LGMD indicates that establishing a putative subtype is possible more than half the time using available diagnostic testing. An efficient approach to genotypic diagnosis is muscle biopsy immunophenotyping followed by directed mutational analysis. The most common LGMDs in the United States are calpainopathies, dysferlinopathies, sarcoglycanopathies, and dystroglycanopathies.
Moore
Steven A
SA
University of Iowa, Iowa City, 52242, USA. steven-moore@uiowa.edu
Shilling
Christopher J
CJ
Westra
Steven
S
Wall
Cheryl
C
Wicklund
Matthew P
MP
Stolle
Catherine
C
Brown
Charlotte A
CA
Michele
Daniel E
DE
Piccolo
Federica
F
Winder
Thomas L
TL
Stence
Aaron
A
Barresi
Rita
R
King
Nick
N
King
Wendy
W
Florence
Julaine
J
Campbell
Kevin P
KP
Fenichel
Gerald M
GM
Stedman
Hansell H
HH
Kissel
John T
JT
Griggs
Robert C
RC
Pandya
Shree
S
Mathews
Katherine D
KD
Pestronk
Alan
A
Serrano
Carmen
C
Darvish
Daniel
D
Mendell
Jerry R
JR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015153:Blotting, Western; D002154:Calpain / Q000172:deficiency; D051242:Caveolin 1 / Q000172:deficiency; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D049030:Dystroglycans / Q000172:deficiency; D005260:Female; D005838:Genotype; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency; D008875:Middle Aged; D009124:Muscle Proteins / Q000172:deficiency; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000145:classification* / Q000235:genetics*; D014481:United States
D051242:Caveolin 1; C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D049030:Dystroglycans; D002154:Calpain