X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1.
Scapuloperoneal (SP) syndrome encompasses heterogeneous neuromuscular disorders characterized by weakness in the shoulder-girdle and peroneal muscles. In a large Italian-American pedigree with dominant SP myopathy (SPM) previously linked to chromosome 12q, we have mapped the disease to Xq26, and, in all of the affected individuals, we identified a missense change (c.365G-->C) in the FHL1 gene encoding four-and-a-half-LIM protein 1 (FHL1). The mutation substitutes a serine for a conserved trypophan at amino acid 122 in the second LIM domain of the protein. Western blot analyses of muscle extracts revealed FHL1 loss that paralleled disease severity. FHL1 and an isoform, FHL1C, are highly expressed in skeletal muscle and may contribute to stability of sarcomeres and sarcolemma, myofibrillary assembly, and transcriptional regulation. This is the first report, to our knowledge, of X-linked dominant SP myopathy and the first human mutation in FHL1.
Quinzii
Catarina M
CM
Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
Vu
Tuan H
TH
Min
K Christopher
KC
Tanji
Kurenai
K
Barral
Sandra
S
Grewal
Raji P
RP
Kattah
Andrea
A
Camaño
Pilir
P
Otaegui
David
D
Kunimatsu
Teruhito
T
Blake
David M
DM
Wilhelmsen
Kirk C
KC
Rowland
Lewis P
LP
Hays
Arthur P
AP
Bonilla
Eduardo
E
Hirano
Michio
M
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D005260:Female; D005799:Genes, Dominant; D050172:Genes, X-Linked; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics*; D060588:LIM Domain Proteins; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D017434:Protein Structure, Tertiary
C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins