1. High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism
- Author
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Yoko Mochizuki, Yuanzhe Li, Manabu Funayama, Kenya Nishioka, Takashi Matsushima, Norimichi Nakamura, Nobutaka Hattori, Chisen Takeuchi, Hiroyo Yoshino, Madoka Mori-Yoshimura, Tatsuhiro Terada, Keiji Ichikawa, Genko Oyama, Tomokazu Obi, Shinji Saiki, Miho Murata, Kazuki Ohi, Yohei Konishi, and Chikara Yamasita
- Subjects
Adult ,Male ,Aging ,medicine.medical_specialty ,Adolescent ,Neurodegeneration with brain iron accumulation ,Neuroaxonal Dystrophies ,Biology ,Infantile neuroaxonal dystrophy ,Young Adult ,WDR45 ,Asian People ,Parkinsonian Disorders ,Intellectual Disability ,Internal medicine ,Intellectual disability ,medicine ,Humans ,Age of Onset ,Child ,Aged ,Genetics ,Genetic heterogeneity ,General Neuroscience ,Parkinsonism ,Neurodegeneration ,Neurodegenerative Diseases ,Middle Aged ,PANK2 ,medicine.disease ,Iron Metabolism Disorders ,Endocrinology ,Child, Preschool ,Mutation ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,Carrier Proteins ,Developmental Biology - Abstract
Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous disorder, characterized by the accumulation of iron in regions such as the basal ganglia. We enrolled 28 patients with childhood intellectual disability and young-onset parkinsonism (≤40 years at onset) and 4 patients with infantile neuroaxonal dystrophy. All had been clinically diagnosed, and the prevalence of genetic mutations linked to NBIA ( PANK2 [exons 1–7], PLA2G6 [exons 2–17], C19orf12 [exons 1–3], WDR45 [exons 2–11], COASY [exons 1–9], FA2H [exons 1–7], and RAB39B [exons 1, 2]) was evaluated. We detected 7 female patients (25.0%, 7 of 28) with de novo heterozygote WDR45 mutations, which are known to be pathogenic for beta-propeller protein-associated neurodegeneration. All 7 patients had common clinical features. Pathogenic mutations in other NBIA genes were not found. We also screened 98 patients with early-onset parkinsonism without intellectual disability and 110 normal controls of Japanese origin for WDR45 mutations. None had WDR45 mutations. Our data suggest a high frequency of beta-propeller protein-associated neurodegeneration mutations in the Japanese population.
- Published
- 2015
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