Open AccessDe novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent families
Author(s) -
Tang Xiaojun,
Lan Xiaoping,
Song Xiaozhen,
Xu Wuhen,
Zhang Yuanfeng,
Zhang Hong,
Wu Shengnan
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - Slovenian
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1499
Subject(s) - dystonia , frameshift mutation , exome sequencing , neurodegeneration , sanger sequencing , parkinsonism , intellectual disability , neurogenetics , nonsense , genetics , epilepsy , medicine , biology , disease , pediatrics , phenotype , mutation , psychiatry , gene
Background Beta‐propeller protein‐associated neurodegeneration (BPAN) is a rare, X‐linked dominant neurodegenerative disease mainly characterized by developmental delay, intellectual disability, epilepsy in childhood and dystonia, parkinsonism, dementia in adulthood. BPAN is caused by variants in WD repeat domain 45(WDR45) , which is characterized by iron accumulation in the basal ganglia, however, it may be atypical in early brain MRI. Methods Whole exome sequencing was performed for five parents‐offspring trios and phenotype‐driven data analyses were conducted. All candidate variants were confirmed by Sanger sequencing. Results Here, we report five independent children presented variable degree of developmental delay, intellectual disability, and/or epilepsy. Five de novo variants of WDR45 including four novel truncating variants (one splicing variant, two nonsense variants, and one frameshift variant) were identified. Although their early brain MRI showed no obvious iron accumulation, multifocal spikes, or polyspikes in electroencephalograms (EEG) were observed in four patients. Conclusion Our study reports four patients with new variants in WDR45 , which expands the mutation spectrum of WDR45 . In addition, our findings provide an early and precise diagnosis basis of BPAN, which is helpful for accurate genetic counseling and prenatal diagnosis.