Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy

被引:91
作者
Tan, P
Briner, J
Boltshauser, E
Davis, MR
Wilton, SD
North, K
Wallgren-Pettersson, C
Laing, NG
机构
[1] Queen Elizabeth II Med Ctr, Australian Neuromuscular Res Inst, Nedlands, WA 6009, Australia
[2] Univ Zurich Hosp, Inst Clin Pathol, CH-8091 Zurich, Switzerland
[3] Univ Zurich, Childrens Hosp, CH-8032 Zurich, Switzerland
[4] Royal Perth Hosp, Dept Neuropathol, Perth, WA, Australia
[5] New Childrens Hosp, Neurogenet Res Unit, Parramatta, NSW 2124, Australia
[6] Univ Helsinki, Dept Med Genet, Helsinki, Finland
[7] Folkhalsan Dept Med Genet, FIN-00251 Helsinki, Finland
基金
英国医学研究理事会;
关键词
alpha-tropomyosin slow; nonsense mutation; recessive nemaline myopathy;
D O I
10.1016/S0960-8966(99)00053-X
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The nemaline myopathies are muscle disorders of variable severity and age of onset, with characteristic nemaline bodies in the sarcoplasm. Genes for dominant (NEM1) and recessive (NEM2A) nemaline myopathy have been localised to chromosomes one and two, respectively. A missense mutation in the alpha-tropomyosin gene (TPM3) has been associated with NEM1 in one family. Probands from 76 other nemaline myopathy families have now been screened for TPM3 mutations. One proband, who was not noted to have any weakness neonatally, but who died at 21 months of age, was shown to be homozygous for a single strand conformation polymorphism (SSCP) in skeletal-muscle-specific exon 1 of TPM3. Sequencing revealed homozygosity for a nonsense mutation at codon 31 (CAG to TAG). The patient should have no functioning alpha-tropomyosin slow protein. The nemaline bodies in this patient were exclusively in type one fibres, consistent with the expression of TPM3 only in type one fibres. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:573 / 579
页数:7
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