Mutational Analysis of COQ2 in Italian Patients with MSA (P5.249)

OBJECTIVES/BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disorder of unknown etiology, clinically characterized by autonomic failure in combination with poorly levodopa responsive parkinsonism, cerebellar dysfunction and pyramidal signs. Recently, mutations in the COQ2 gene have been identified as causative in familial autosomal recessive MSA. COQ2 encoded product catalyzes one of the final reactions in the biosynthesis of CoQ10, a redox carrier in the mitochondrial respiratory chain. We aim to screen COQ2 in our MSA dataset. METHODS: We performed a sequencing analysis of the COQ2 gene (NM_015697.7) in 14 patients with a diagnosis of probable MSA-P (2 familiar and 12 apparently sporadic) and 6 sporadic patients with MSA-C. RESULTS: The homozygous Ala43Gly change and the heterozygous Asn180Ser mutation were disclosed in two sporadic patients with MSA-C, but not in matched controls. The variants lie within or nearby the UbiA substrate-binding site of COQ2 enzyme and are predicted pathogenetic according several algorithm including Polyphen2, Mutation Taster and SIFT. The refined characterization of COQ2 transcript in human tissues as well as functional analyses to investigate the pathogenetic role of the disclosed variants is currently ongoing. CONCLUSIONS: Overall, these findings support the hypothesis that COQ2 variants may represent a rare but relevant cause of MSA even in the Italian population. Further studies are required to address the role of COQ2 and CoQ10 availability in MSA. Disclosure: Dr. Ronchi has nothing to disclose. Dr. Bonato has nothing to disclose. Dr. Di Biase has nothing to disclose. Dr. Melzi has nothing to disclose. Dr. Trezzi has nothing to disclose. Dr. Corti has nothing to disclose. Dr. Bresolin has nothing to disclose. Dr. Comi has nothing to disclose. Dr. Di Fonzo has nothing to disclose.