P.44 - A case of severe encephalopathy and movement disorder due to mutations in the TRAPPC11 gene

Abstract

TRAPPC11 is a component of the transport protein particle complex (TRAPPC) which mediates trafficking of vesicles from the endoplasmic reticulum to the Golgi system. Recently mutations in TRAPPC11 have been described in patients with neurological and neuromuscular diseases ranging from congenital muscular dystrophy to limb-girdle-muscular dystrophy and myopathy with ataxia and intellectual disability. Here we report the case of a 7 years old child with a severe myopathy, central nervous system involvement cause by mutations in TRAPPC11 gene. The patient presented with hypotonia, spasticity and abnormal involuntary movements (hyperkinesia and stereotypia movements ). He was born with microcephaly and showed cortical atrophy on brain MRI. He was never able to stand or walk. He has a severe cognitive delay. Serum CK levels were elevated ( 350 - 2817 UI/L nr < 190). Muscle biopsy performed at the age of 4 showed myopathic changes, reduction of cytochrome c activity in some fibres and normal expression of sarcolemmal proteins except for a mild reduction of α-dystroglycan in some fibres.The patient was included in the MYO-SEQ project and his DNA studied by Whole-exome-sequencing. Two compound heterozygous mutations were identified in the TRAPPC1 gene. One of them has been previously described (c.1287 +5G>A) and results in the skipping of exons 11 and 12 and an in frame deletion of 58 aa. The second mutation (c.3379_3380insT) has not been reported before and is predicted to cause a frameshift in the open reading frame and premature termination of the protein near the C-terminus. Each mutation has been inherited from one of the non-affected parents.TRAPPC11 protein was significantly reduced in the patient's fibroblasts which supports that the identified mutations in the TRAPPC11 gene is the disease cause. Discussion: This case expands the phentotypic and genetic spectrum of TRAPPC11 associated myopathies. TRAPPC11 should be considered in the differential diagnosis of patients with myopathy/movement disorder, elevated CK and central nervous system involvement.