De novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent families. Issue 11 (10th October 2020)

• Record Type: Journal Article
• Authors: Tang, Xiaojun; Lan, Xiaoping; Song, Xiaozhen; Xu, Wuhen; Zhang, Yuanfeng; Zhang, Hong; Wu, Shengnan
• Is Part Of: Molecular genetics & genomic medicine. Volume 8:Issue 11(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-10
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1499
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: 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. Abstract : Our study reports five de novo variants with BPAN including four new variants in five independent non‐consanguineous Chinese families, which enlarges the mutation spectrum of WDR45. The application of trio exome sequencing contributes to the early detection of BPAN, which can help patients get timely genetic counseling preventing the disease from worsening and open the way for preimplantation genetic diagnosis and future prenatal check‐ups.