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

The nemaline myopathies are muscle disorders of variable severity and age o f onset, with characteristic nemaline bodies in the sarcoplasm. Genes for d ominant (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. Proban ds 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 s low protein. The nemaline bodies in this patient were exclusively in type o ne fibres, consistent with the expression of TPM3 only in type one fibres. (C) 1999 Elsevier Science B.V. All rights reserved.