Objective: To investigate the clinical features and identify the disease-causing gene in a black South African family affected by juvenile-onset parkinsonism and intellectual disability.

Background: The genetic bases of Parkinson’s disease (PD) in Sub-Saharan African (SSA) populations are poorly characterized, and analysis of SSA families might lead to the discovery of novel disease genes associated with PD.

Methods: Clinical evaluation, neuroimaging studies, homozygosity mapping, whole-exome sequencing analysis, and Sanger sequencing of selected candidate variants.

Results: Identification of a homozygous 28-nucleotides frameshift deletion in PTRHD1 coding region that segregates with disease in the affected family and reached significant two-point LOD score. PTRHD1 was recently nominated as the disease-causing gene in two Iranian families with a similar phenotype, who carry homozygous missense mutations.

Conclusions: Here, by genome-wide unbiased methods, we provide conclusive evidence that loss-of-function mutations in PTRHD1 cause a novel monogenic form of autosomal recessive juvenile parkinsonism and intellectual disability.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ptrhd1-loss-of-function-mutation-in-an-african-family-with-parkinsonism-and-intellectual-disability/