CORE-ROD MYOPATHY CAUSED BY MUTATIONS IN THE NEBULIN GENE

Nemaline myopathy (NM) and central core disease (CCD), 2 of the most frequent congenital myopathies, are clinically and genetically heterogeneous disorders of skeletal muscle. NM (OMIM 161800) is caused by mutations in at least 6 different genes encoding thin filament proteins of the striated muscle sarcomere: skeletal alpha-actin (ACTA1), nebulin (NEB), beta-tropomyosin (TPM2), slow alpha-tropomyosin (TPM3), slow skeletal muscle troponin-T (TNNT1), and cofilin-2 (CFL2). CCD (OMIM 117000) is mainly caused by mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1), a Ca²⁺ channel involved in excitation-contraction coupling. Congenital myopathies with the combination of distinct “cores” and “rods” in the same muscle fibers have been described in a small number of cases. In 2 families mutations have been identified in RYR1^1,2 and in others, linkage has been found to a locus on chromosome 15.³

Here we report a patient with recessively inherited core-rod myopathy caused by compound heterozygous mutations in NEB. This observation broadens the spectrum of genes involved in core-rod myopathies.