Early manifestations of epileptic encephalopathy, brain atrophy, and elevation of serum neuron specific enolase in a boy with beta-propeller protein-associated neurodegeneration

Kyoko Takano, Kazuya Goto, Mitsuo Motobayashi, Keiko Wakui, Rie Kawamura, Tomomi Yamaguchi, Yoshimitsu Fukushima, Tomoki Kosho

Research output: Contribution to journalArticle

6 Citations (Scopus)


Mutations in WDR45 are responsible for beta-propeller protein-associated neurodegeneration (BPAN), which is an X-linked form of neurodegeneration with brain iron accumulation. BPAN mainly affects females and is characterized by seizures and developmental delay or intellectual disability until adolescence or early adulthood, followed by severe dystonia, parkinsonism, and progressive dementia. However, rare male patients have recently been reported with hemizygous germline mutations in WDR45 and severe clinical manifestations, such as epileptic encephalopathies. We report here a 4-year-old boy presenting with profound developmental delay, non-syndromic epileptic encephalopathy, and early brain atrophy. The level of serum neuron specific enolase (NSE) was elevated, but the level of serum phosphorylated neurofilament heavy chain was not detectable. Targeted next-generation sequencing identified a de novo hemizygous splice donor site mutation, c.830+1G > A in WDR45, which resulted in a splicing defect evidenced by reverse transcriptase-PCR. Mutations in WDR45 should be considered as a cause for epileptic encephalopathies in males with profound developmental delay and brain atrophy. Furthermore, elevation of serum NSE may contribute to early diagnosis of BPAN.

Original languageEnglish
Pages (from-to)521-526
Number of pages6
JournalEuropean Journal of Medical Genetics
Issue number10
Publication statusPublished - 10-2017


All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this