title: Limb-girdle muscular dystrophy in the United States.
abstract: 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.
authors.affiliation: University of Iowa, Iowa City, 52242, USA. steven-moore@uiowa.edu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Shilling
authors.forename: Steven
authors.initials: S
authors.lastname: Westra
authors.forename: Cheryl
authors.initials: C
authors.lastname: Wall
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Wicklund
authors.forename: Catherine
authors.initials: C
authors.lastname: Stolle
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Brown
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Michele
authors.forename: Federica
authors.initials: F
authors.lastname: Piccolo
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Winder
authors.forename: Aaron
authors.initials: A
authors.lastname: Stence
authors.forename: Rita
authors.initials: R
authors.lastname: Barresi
authors.forename: Nick
authors.initials: N
authors.lastname: King
authors.forename: Wendy
authors.initials: W
authors.lastname: King
authors.forename: Julaine
authors.initials: J
authors.lastname: Florence
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Fenichel
authors.forename: Hansell H
authors.initials: HH
authors.lastname: Stedman
authors.forename: John T
authors.initials: JT
authors.lastname: Kissel
authors.forename: Robert C
authors.initials: RC
authors.lastname: Griggs
authors.forename: Shree
authors.initials: S
authors.lastname: Pandya
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Mathews
authors.forename: Alan
authors.initials: A
authors.lastname: Pestronk
authors.forename: Carmen
authors.initials: C
authors.lastname: Serrano
authors.forename: Daniel
authors.initials: D
authors.lastname: Darvish
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mendell
mesh_terms: 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
chemical_list: D051242:Caveolin 1; C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D049030:Dystroglycans; D002154:Calpain