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

Introduction: Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations. Objectives: We aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism. Methods: Full phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members. Results: The 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. Conclusion: Given 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.