Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation.
We investigated a large German family (n = 37) with male members who had contractures, rigid spine syndrome, and hypertrophic cardiomyopathy. Muscle weakness or atrophy was not prominent in affected individuals. Muscle biopsy disclosed a myopathic pattern with cytoplasmic bodies. We used microsatellite markers and found linkage to a locus at Xq26-28, a region harboring the FHL1 gene. We sequenced FHL1 and identified a new missense mutation within the third LIM domain that replaces a highly conserved cysteine by an arginine (c.625T>C; p.C209R). Our finding expands the phenotypic spectrum of the recently identified FHL1-associated myopathies and widens the differential diagnosis of Emery-Dreifuss-like syndromes.
Knoblauch
Hans
H
Muscle Research Unit, Experimental and Clinical Research Center, Charité University Medicine Berlin, Germany.
Geier
Christian
C
Adams
Stephanie
S
Budde
Birgit
B
Rudolph
André
A
Zacharias
Ute
U
Schulz-Menger
Jeannette
J
Spuler
Andreas
A
Yaou
Rabah Ben
RB
Nürnberg
Peter
P
Voit
Thomas
T
Bonne
Gisele
G
Spuler
Simone
S
D000293:Adolescent; D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology; D002648:Child; D003286:Contracture / Q000235:genetics* / Q000473:pathology; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005858:Germany; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D060588:LIM Domain Proteins; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012737:Sex Factors; D055815:Young Adult
C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins