CORE-ROD MYOPATHY CAUSED BY MUTATIONS IN THE NEBULIN GENE

Abstract

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. ### Case report. The patient is a 27-year-old white man. He presented at birth with generalized hypotonia and required immediate intubation and resuscitation. Spontaneous movements were very poor and he had seizures from the first week. Restrictive respiratory insufficiency led to continuous mechanical ventilation via tracheotomy at the age of 2 years. The patient did not acquire independent walking but was able to take a few steps with orthosis at the age of 4; diffuse muscle weakness with axial predominance was observed. Electromyography showed myopathic patterns and normal motor and sensory responses. Serum creatine kinase levels were normal. The patient developed …