FATAL HYPERTROPHIC CARDIOMYOPATHY AND NEMALINE MYOPATHY ASSOCIATED WITH ACTA1 K336E MUTATION

We report on a 2-year-old male child with both nemaline myopathy and hypertrophic cardiomyopathy (HCM). Sequencing of the ACTA1 gene showed a ‘‘de novo’’ missense heterozygous mutation a > g in exon 7 (Lys336Glu). Two-dimensional electrophoresis showed 28% mutant actin present in his muscle biopsy. Actin was isolated from the muscle biopsy and examined by in vitro motility assay. The sliding speed was 13 ± 3% less than normal and the affinity of actin for the Z-line protein a-actinin was reduced 10 fold. This is the first report on a hypertrophic cardiomyopathy associated with nemaline myopathy and an ACTA1 mutation. 2006 Elsevier B.V. All rights reserved.