PTRHD1 Loss-of-function mutation in an african family with juvenile-onset Parkinsonism and intellectual disability

Autor: Demy J S, Kuipers, Jonathan, Carr, Soraya, Bardien, Pearl, Thomas, Boiketlo, Sebate, Guido J, Breedveld, Rick, van Minkelen, Rutger W W, Brouwer, Wilfred F J, van Ijcken, Marjon A, van Slegtenhorst, Vincenzo, Bonifati, Marialuisa, Quadri
Rok vydání: 2018
Předmět:
Zdroj: Movement disorders : official journal of the Movement Disorder Society. 33(11)
ISSN: 1531-8257
Popis: The genetic bases of PD in sub-Saharan African (SSA) populations remain poorly characterized, and analysis of SSA families with PD might lead to the discovery of novel disease-related genes.To investigate the clinical features and identify the disease-causing gene in a black South African family with 3 members affected by juvenile-onset parkinsonism and intellectual disability.Clinical evaluation, neuroimaging studies, whole-exome sequencing, homozygosity mapping, two-point linkage analysis, and Sanger sequencing of candidate variants.A homozygous 28-nucleotide frameshift deletion in the PTRHD1 coding region was identified in the 3 affected family members and linked to the disease with genome-wide significant evidence. PTRHD1 was recently nominated as the disease-causing gene in two Iranian families, each containing 2 siblings with similar phenotypes and homozygous missense mutations.Together with the previous reports, we provide conclusive evidence that loss-of-function mutations in PTRHD1 cause autosomal-recessive juvenile parkinsonism and intellectual disability. © 2018 International Parkinson and Movement Disorder Society.
Databáze: OpenAIRE
Externí odkaz: