Abstract
Background: Ataxia with Vitamin E deficiency (AVED) is a type of autosomal recessive cerebellar ataxia. The main clinical manifestation involves progressive cerebellar ataxia and movement disorders, α-tocopherol transfer protein(TTPA) gene mutations are responsible for this disease. Methods: A female patient from a consanguineous Chinese family underwent detailed physical and auxiliary examination. After exclusion of acquired causes of ataxia, Friedreich’s Ataxia, and common types of spinocerebellar ataxia, the patient was subjected to whole exome sequencing (WES) followed by confirmation of sequence variants using Sanger sequencing. Her asymptomatic parents and younger sister were genotyped for the variant. Results: This patient showed progressive cerebellar ataxia, dysarthria and dystonic tremor, her serum vitamin E concentration was remarkably decreased, brain MRI revealed no obvious cerebellum atrophy. Homozygous variant (c.473T>C, p.F158S) of TPPA gene were identified through WES. Bioinformatic analysis predicted F185S would be harmful to the protein function. After supplementation of vitamin E 400mg three times per day for two years, the patient’s symptom remained stabilization.Conclusions We identified an AVED patient caused by novel mutation in TTPA gene. Our findings widen the spectrum of TTPA gene mutations.
Crystal structure of human -tocopherol transfer protein bound to its ligand: Implications for ataxia with vitamin E deficiency