title: De novo missense mutation in a constitutively expressed exon of the slow alpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy.
abstract: We describe an atypical case of nemaline myopathy with an unusual distribution of muscle weakness who presented at 14 years of age with kyphoscoliosis. In this patient, we demonstrate heterozygosity for a de novo CGT-CAT (Arg167His) mutation in a constitutively expressed exon (exon 5) of slow alpha-tropomyosin (TPM3). This is the first mutation identified in a constitutively expressed exon of TPM3 in a nemaline myopathy patient, but is similar to recently described mutations in beta-tropomyosin (TPM2) associated with nemaline myopathy and mutations in fast alpha-tropomyosin (TPM1) which cause hypertrophic cardiomyopathy.
authors.affiliation: Neurogenetics Laboratory, Royal Perth Hospital, Western Australia, Perth, Australia.
authors.forename: H J
authors.initials: HJ
authors.lastname: Durling
authors.forename: P
authors.initials: P
authors.lastname: Reilich
authors.forename: J
authors.initials: J
authors.lastname: Müller-Höcker
authors.forename: B
authors.initials: B
authors.lastname: Mendel
authors.forename: D
authors.initials: D
authors.lastname: Pongratz
authors.forename: C
authors.initials: C
authors.lastname: Wallgren-Pettersson
authors.forename: P
authors.initials: P
authors.lastname: Gunning
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
authors.forename: N G
authors.initials: NG
authors.lastname: Laing
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000293:Adolescent; D001120:Arginine / Q000235:genetics; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D005091:Exons; D005260:Female; D006580:Genetic Carrier Screening; D006639:Histidine / Q000235:genetics; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D018908:Muscle Weakness / Q000209:etiology / Q000235:genetics; D020125:Mutation, Missense; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000503:physiopathology / Q000648:ultrastructure; D014335:Tropomyosin / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C490775:TPM1 protein, human; C498783:TPM3 protein, human; C097163:Tm2 protein, Drosophila; C490774:Tpm1 protein, mouse; D014335:Tropomyosin; D006639:Histidine; D001120:Arginine; D000251:Adenosine Triphosphatases