PTRHD1 Loss-of-function mutation in an african family with juvenile-onset Parkinsonism and intellectual disability
| Autor: | Vincenzo Bonifati, Jonathan Carr, Rick van Minkelen, Wilfred F. J. van IJcken, Guido J. Breedveld, Demy J.S. Kuipers, Rutger W W Brouwer, Boiketlo Sebate, Marialuisa Quadri, Pearl Thomas, Marjon van Slegtenhorst, Soraya Bardien |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetics Sanger sequencing Parkinsonism Disease Biology medicine.disease Disease gene identification Frameshift mutation 03 medical and health sciences symbols.namesake 030104 developmental biology 0302 clinical medicine Neurology Genetic linkage Intellectual disability medicine symbols Missense mutation Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Movement Disorders. 33:1814-1819 |
| ISSN: | 0885-3185 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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