title: Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation.
abstract: 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.
authors.affiliation: Muscle Research Unit, Experimental and Clinical Research Center, Charité University Medicine Berlin, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Knoblauch
authors.forename: Christian
authors.initials: C
authors.lastname: Geier
authors.forename: Stephanie
authors.initials: S
authors.lastname: Adams
authors.forename: Birgit
authors.initials: B
authors.lastname: Budde
authors.forename: André
authors.initials: A
authors.lastname: Rudolph
authors.forename: Ute
authors.initials: U
authors.lastname: Zacharias
authors.forename: Jeannette
authors.initials: J
authors.lastname: Schulz-Menger
authors.forename: Andreas
authors.initials: A
authors.lastname: Spuler
authors.forename: Rabah Ben
authors.initials: RB
authors.lastname: Yaou
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Gisele
authors.initials: G
authors.lastname: Bonne
authors.forename: Simone
authors.initials: S
authors.lastname: Spuler
mesh_terms: 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
chemical_list: C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins