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Neurobiol Aging. 2015 May;36(5):2004.e9-2004.e15. doi: 10.1016/j.neurobiolaging.2015.01.020. Epub 2015 Jan 30.

High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism.

Author information

1
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
2
Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
3
Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan.
4
Department of Neurology, National Centre Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
5
Department of Neurology, Kyushu University Hospital, Fukuoka, Japan.
6
Department of Neurology, Yotsukaidou Tokushukai Medical Center, Chiba, Japan.
7
Department of Neurology, Hyogo Prefectural Amagasaki Hospital, Hyogo, Japan.
8
Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
9
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
10
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp.

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.

KEYWORDS:

Beta-propeller protein-associated neurodegeneration; Intellectual disability; Neurodegeneration with brain iron accumulation; Parkinsonism; WDR45

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