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PTRHD1 Loss‐of‐function mutation in an african family with juvenile‐onset Parkinsonism and intellectual disability
Author(s) -
Kuipers Demy J.S.,
Carr Jonathan,
Bardien Soraya,
Thomas Pearl,
Sebate Boiketlo,
Breedveld Guido J.,
van Minkelen Rick,
Brouwer Rutger W.W.,
van Ijcken Wilfred F.J.,
van Slegtenhorst Marjon A.,
Bonifati Vincenzo,
Quadri Marialuisa
Publication year - 2018
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.27501
Subject(s) - parkinsonism , genetics , exome sequencing , frameshift mutation , missense mutation , intellectual disability , sanger sequencing , biology , candidate gene , disease , disease gene identification , loss function , mutation , gene , phenotype , medicine , pathology
Background : 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. Objectives : 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. Methods : Clinical evaluation, neuroimaging studies, whole‐exome sequencing, homozygosity mapping, two‐point linkage analysis, and Sanger sequencing of candidate variants. Result : 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. Conclusion : 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