Published on Oct 1, 2014in Neuromuscular Disorders3.115
· DOI :10.1016/J.NMD.2014.06.343
Nebulin is a giant sarcomeric protein spanning whole length of thin filament, and its coding gene (NEB) mostly causes autosomal recessive nemaline myopathy. The NEB mutations may also cause distal nebulin myopathy with initial presentation of foot drop, and recent reports added another muscle disease of core-rod myopathy with double presentation of nemaline rods and cores. In this study, two patients with nemaline rods in muscle pathology were recruited, one of whom (patient 1) was the proband of a symptomatic sibling. Patient 1 initially presented with foot drop and has been a slow runner since childhood. His fourth elder brother also complained of foot drop and gait disturbance. Patient 2 had gait disturbance since age 5, and his ankle dorsiflexors were the most weak among all muscles. All the patients were still ambulant and never complained of respiratory restriction. Muscle CT scans revealed atrophy of anterior tibial muscles in both of patients. Muscle pathology additionally showed core lesions and mitochondrial abnormalities, as well as nemaline rods. Nemaline myopathy-causing genes were first excluded and then, whole exome sequencing and followed targeted sequencing were detected three novel mutations in NEB gene: one missense, one single bp deletion and del/ins mutations. One missense mutation was shared by all of them. This study represents the disease associated with novel NEB mutations marked by the presence of additional pathological features, as well as nemaline rods. Although mixed pathology has been already reported in core-rod myopathy with NEB mutations, muscle pathology in these patients is more characteristic, and clinical manifestation is much milder compared with the previous ones. This report suggests the expanded clinical and pathological spectrum of nebulin-associated myopathy with new genetic and pathologic features. Further, next genome sequencing might be helpful for searching mutations in big, huge-sized genes, such as NEB.