Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy.
Nemaline myopathy is a clinically and genetically heterogeneous muscle disorder. In the nebulin gene we have detected a number of autosomal recessive mutations. Both autosomal dominant and recessive mutations have been detected in the genes for alpha-actin and alpha-tropomyosin 3. A recessive mutation causing nemaline myopathy among the Old Order Amish has recently been identified in the gene for slow skeletal muscle troponin T. As linkage studies had shown that at least one further gene exists for nemaline myopathy, we investigated another tropomyosin gene expressed in skeletal muscle, the beta-tropomyosin 2 gene. Screening 66 unrelated patients, using single strand conformation polymorphism analysis and sequencing, we found four polymorphisms and two heterozygous missense mutations. Both mutations affect conserved amino acids, and in both cases, the mutant allele is expressed. We speculate that the observed mutations affect the formation of the tropomyosin dimer and its actin-binding properties.
Donner
Kati
K
Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
Ollikainen
Miina
M
Ridanpää
Maaret
M
Christen
Hans-Jürgen
HJ
Goebel
Hans H
HH
de Visser
Marianne
M
Pelin
Katarina
K
Wallgren-Pettersson
Carina
C
D000595:Amino Acid Sequence; D000818:Animals; D001706:Biopsy; D017931:DNA Primers; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D020125:Mutation, Missense; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011487:Protein Conformation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014335:Tropomyosin / Q000737:chemistry / Q000235:genetics*
D017931:DNA Primers; D005819:Genetic Markers; D014335:Tropomyosin