Majczenko et al. (2012) reported a family in which 5 individuals had early-onset myopathy. Features included neonatal hypotonia or increased falls with distal more than proximal muscle involvement, myalgias, and mild to moderate overall motor impairment. Ambulation was ... Majczenko et al. (2012) reported a family in which 5 individuals had early-onset myopathy. Features included neonatal hypotonia or increased falls with distal more than proximal muscle involvement, myalgias, and mild to moderate overall motor impairment. Ambulation was preserved, and the face, extraocular, cardiac, and respiratory muscles were not affected. Most patients had mild cognitive impairment requiring special education. Skeletal muscle biopsy from the 5-year-old proband showed type 1 fiber predominance, fiber-size variability, centralized nuclei, and core-like areas. Immunostaining showed actin- and desmin-positive aggregates. Electron microscopic studies showed a disrupted contractile apparatus, loss of the normal sarcomeric striation, Z-band streaming, sparse or absent mitochondria in the center of the lesion with secondary mitochondrial accumulation at the periphery, and distention of transverse-tubules. Biopsy from a 10-month-old patient showed fiber-type variability and increased central nuclei, as well as desmin and actin immunoreactive aggregates. The pathologic diagnosis was reported as a congenital myopathy with prominent internal nuclei, atypical core-like lesions, and desmin-positive aggregates.
In affected members of a family with centronuclear myopathy-4, Majczenko et al. (2012) identified a heterozygous mutation in the CCDC78 gene (614666.0001). The mutation was found by linkage analysis followed by whole-exome capture and next-generation gene sequencing. Expression ... In affected members of a family with centronuclear myopathy-4, Majczenko et al. (2012) identified a heterozygous mutation in the CCDC78 gene (614666.0001). The mutation was found by linkage analysis followed by whole-exome capture and next-generation gene sequencing. Expression of the mutation in the ortholog of developing zebrafish resulted in multiple abnormalities, including bent backs and shortened tails. Mutant zebrafish also showed abnormal motor behavior, ranging from impaired swimming to a complete lack of movement. Mutant zebrafish myofibers showed aberrantly aggregated clusters of Ccdc78 and dilated sarcoplasmic reticulum and T-tubules. Mutations in the CCDC78 gene were not found in 46 additional probands with congenital myopathy, suggesting that mutations in this gene are not common.