BPAN. The Only X-Linked Dominant NBIA Disorder

Tobias B. Haack, Penelope (Penny) Hogarth, Allison Gregory, Holger Prokisch, Susan Hayflick

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Beta-propeller protein-associated neurodegeneration (BPAN) is the most recently identified subtype of neurodegeneration with brain iron accumulation (NBIA), being unique with respect to the underlying disease genetics, the associated clinical presentation, and the suggested pathomechanism. Mutations in X-chromosomal WDR45 arise de novo; however, the dominant pattern of inheritance is unusual for an X-linked disorder and additional mechanisms such as X-inactivation or somatic mosaicism are likely to contribute to the phenotype that is indistinguishable between males and females. The course of the disease is two-staged with developmental delay and intellectual disability in childhood and a second phase of rapid neurological deterioration characterized by parkinsonism and dementia occurring in adolescence or early adulthood. At this time, neuroimaging findings are characteristic and provide excellent diagnostic guidance. There is increasing evidence that human WDR45 deficiency impairs autophagy, thereby raising the possibility that this rare disorder will offer insights into more common neurodegenerative disorders such as Parkinson or Alzheimer disease.

Original languageEnglish (US)
Pages (from-to)85-90
Number of pages6
JournalInternational Review of Neurobiology
Volume110
DOIs
StatePublished - 2013

Fingerprint

X Chromosome Inactivation
Inheritance Patterns
Developmental Disabilities
Inborn Genetic Diseases
Mosaicism
Autophagy
Parkinsonian Disorders
Neuroimaging
Intellectual Disability
Neurodegenerative Diseases
Parkinson Disease
Dementia
Alzheimer Disease
Phenotype
Mutation
Proteins
Neurodegeneration with brain iron accumulation (NBIA)

Keywords

  • Autophagy
  • De novo mutations
  • Dyskinesia
  • Intellectual disability
  • Parkinsonism
  • Rett-like
  • WDR45
  • X-linked

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

BPAN. The Only X-Linked Dominant NBIA Disorder. / Haack, Tobias B.; Hogarth, Penelope (Penny); Gregory, Allison; Prokisch, Holger; Hayflick, Susan.

In: International Review of Neurobiology, Vol. 110, 2013, p. 85-90.

Research output: Contribution to journalArticle

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