Early-onset parkinsonism with intellectual disability in an Italian family associated with a PTRHD1 variant

Background: Mutations in PTRHD1 have recently been implicated in autosomal recessive neurodevelopmental syndromes characterized by intellectual disability, and variably penetrant early-onset parkinsonism, mainly in consanguineous families of Middle Eastern or African origin. Objectives: To describe the clinical and genetic findings of the first Italian family carrying a homozygous PTRHD1 nonsense mutation associated with early-onset parkinsonism and intellectual disability. Methods: A 45-gene Parkinson's disease panel was analyzed by targeted next-generation sequencing in a proband, a 32-year-old female with moderate intellectual disability and early-onset parkinsonism. Results: The analysis revealed a homozygous nonsense variant (c.213C > A, p.Tyr71*), segregating with severe intellectual disability and variably penetrant parkinsonian features in the proband's paternal cousin and his father. Conclusions: This study expands the mutational and geographical spectrum of PTRHD1-related disorders and reinforces the inclusion of PTRHD1 in genetic screening panels for early-onset parkinsonism, particularly in individuals with intellectual disability and evidence of autosomal recessive inheritance.