G.P.155: A first Asian MEGF10 myopathy due to novel homozygous mutation

Abstract

Recessive mutations in Multiple epidermal growth factor-like domains 10 (MEGF10) are known to cause the syndrome of early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). We found a novel <i>MEGF10</i> mutation by whole exome sequencing (WES) in a Japanese patient with EMRDD. The patient is a 9-year-old boy from a non-consanguineous family. There is no family history of neuromuscular disease. He was born at 39 weeks of gestational age. Although peri- and neonatal periods were uneventful, he had frequent respiratory infections in early infancy. At age 1 year and 6 months he developed respiratory failure for which mechanical ventilation was necessary, in addition to facial and limbs muscle weakness, finger joint contracture, and areflexia. Muscle biopsy at age 1 year and 9 months showed unspecific changes with moderate fiber size variation and type 2 fiber atrophy. At age 2 years NIPPV was started. He could stand alone at 2 years and 5 months, walk alone at 2 years and 9 months old. At age 9 years he was found to have proximal muscle weakness with Gowers' sign, although he was still ambulant. Scoliosis was also developed. Serum CK levels were normal. Second muscle biopsy at age 9 years revealed marked fiber size variation, moth-eaten appearance in some fibers, adipose tissue infiltration, and endomysial fibrosis, reflecting chronic progressive course of myopathic disease. WES identified a homozygous frameshift mutation (c.129_130delTG p.Thr43 fsX9). On western blotting MEGF10 was absent in the patient's muscle, whereas it was increased in DMD muscle. Together with clinical and pathological manifestations compatible with EMARDD, we concluded that the disease is caused by <i>MEGF10</i> mutation in the patient. This is the first report of Asian EMARDD.