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

2016; Wiley; Volume: 32; Issue: 2 Linguagem: Inglês

10.1002/mds.26824

1531-8257

Hamidreza Khodadadi, Luís Azcona, Vajiheh Aghamollaii, Mir Davood Omrani, Masoud Garshasbi, Shaghayegh Taghavi, Abbas Tafakhori, Gholam Ali Shahidi, Javad Jamshidi, Hossein Darvish, Coro Paisán‐Ruiz,

Wnt/β-catenin signaling in development and cancer

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. © 2016 International Parkinson and Movement Disorder Society.