High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism.
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.
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Kenya
K
Nishioka
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Genko
G
Oyama
Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Hiroyo
H
Yoshino
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Yuanzhe
Y
Li
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Takashi
T
Matsushima
Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan.
Chisen
C
Takeuchi
Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo, Japan.
Yoko
Y
Mochizuki
Department of Neurology, National Centre Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Madoka
M
Mori-Yoshimura
Department of Neurology, National Centre Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Miho
M
Murata
Department of Neurology, Kyushu University Hospital, Fukuoka, Japan.
Chikara
C
Yamasita
Department of Neurology, Kyushu University Hospital, Fukuoka, Japan.
Norimichi
N
Nakamura
Department of Neurology, Yotsukaidou Tokushukai Medical Center, Chiba, Japan.
Yohei
Y
Konishi
Department of Neurology, Hyogo Prefectural Amagasaki Hospital, Hyogo, Japan.
Kazuki
K
Ohi
Department of Neurology, Hyogo Prefectural Amagasaki Hospital, Hyogo, Japan.
Keiji
K
Ichikawa
Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Tatsuhiro
T
Terada
Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Tomokazu
T
Obi
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.
Manabu
M
Funayama
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Shinji
S
Saiki
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.
Nobutaka
N
Hattori
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D019189:Iron Metabolism Disorders / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019150:Neuroaxonal Dystrophies / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
D002352:Carrier Proteins; C578284:WDR45 protein, human
Beta-propeller protein-associated neurodegeneration; Intellectual disability; Neurodegeneration with brain iron accumulation; Parkinsonism; WDR45