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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Asian Continental Ancestry Group
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Intellectual Disability / complications
  • Intellectual Disability / epidemiology
  • Intellectual Disability / genetics*
  • Iron Metabolism Disorders / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Neuroaxonal Dystrophies / complications
  • Neuroaxonal Dystrophies / epidemiology
  • Neuroaxonal Dystrophies / genetics*
  • Neurodegenerative Diseases / complications
  • Neurodegenerative Diseases / epidemiology
  • Neurodegenerative Diseases / genetics*
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / epidemiology
  • Parkinsonian Disorders / genetics*
  • Young Adult

Substances

  • Carrier Proteins
  • WDR45 protein, human

Supplementary concepts

  • Neurodegeneration with brain iron accumulation (NBIA)