Abstract
Rigid spine muscular dystrophy 1 (RSMD1) is a neuromuscular disorder, manifested with poor axial muscle strength, scoliosis and neck weakness, and a variable degree of spinal rigidity with an early ventilatory insufficiency which can lead to death by respiratory failure. Mutations of SEPN1 gene are associated with autosomal recessive RSMD1. Here, we present a clinical molecular study of a Chinese proband with RSMD1. The proband is a 17 years old male, showing difficulty in feeding, delayed motor response, problem in running with frequent fall down, early onset respiratory insufficiency, general muscle weakness and rigid cervical spine. Muscle biopsy identified increased variability of fiber size with atrophic muscle cells consistent with non-specific myopathic changes. Proband's elder brother presented with same phenotype as the proband and died at the age of 15 years due to acute respiratory failure. Proband's father and mother are phenotypically normal. Targeted exome capture based next generation sequencing and Sanger sequencing identified that the proband was a compound heterozygote with two novel mutations in SEPN1 gene; a novel missense mutation (c.1384T>C; p.Sec462Arg) and a novel nonsense mutation (c.1525C>T; p.Gln509Ter), inherited from his father and mother respectively. These two mutations are co-segregated with the disease phenotypes in the proband and was absent in normal healthy controls. Our present study expands the mutational spectrum of the SEPN1 associated RSMD1.