PTRHD1 (C2orf79) mutations lead to autosomal-recessive intellectual disability and parkinsonism.

IntroductionAtypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations. ObjectivesWe aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism. MethodsFull phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members. ResultsThe chromosome, 2p23.3, was identified as the disease-associated locus, and a homozygous PTRHD1 mutation (c.157C>T) was then established as the disease-causing mutation. The pathogenicity of this PTRHD1 mutation was supported by its segregation with the disease status, its location in a functional domain of the encoding protein, as well as its absence in public databases and ethnicity-matched control chromosomes. ConclusionGiven the role of 2p23 locus in patients with intellectual disability and the previously reported PTRHD1 mutation (c.155G>A) in patients with parkinsonism and cognitive dysfunction, we concluded that the PTRHD1 mutation identified in this study is likely to be responsible for the phenotypic features of the family under consideration. (c) 2016 International Parkinson and Movement Disorder Society.