De novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent families
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 varia...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-11-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Online Access: | https://doi.org/10.1002/mgg3.1499 |
| _version_ | 1797301008161832960 |
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| author | Xiaojun Tang Xiaoping Lan Xiaozhen Song Wuhen Xu Yuanfeng Zhang Hong Zhang Shengnan Wu |
| author_facet | Xiaojun Tang Xiaoping Lan Xiaozhen Song Wuhen Xu Yuanfeng Zhang Hong Zhang Shengnan Wu |
| author_sort | Xiaojun Tang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T23:16:07Z |
| format | Article |
| id | doaj.art-99ff39782a7c4bb98b6444b17e4e0fb3 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:16:07Z |
| publishDate | 2020-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-99ff39782a7c4bb98b6444b17e4e0fb32024-02-21T11:47:09ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-11-01811n/an/a10.1002/mgg3.1499De novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent familiesXiaojun Tang0Xiaoping Lan1Xiaozhen Song2Wuhen Xu3Yuanfeng Zhang4Hong Zhang5Shengnan Wu6Molecular Diagnostic Laboratory Shanghai Children's Hospital Shanghai Jiaotong University Shanghai ChinaMolecular Diagnostic Laboratory Shanghai Children's Hospital Shanghai Jiaotong University Shanghai ChinaMolecular Diagnostic Laboratory Shanghai Children's Hospital Shanghai Jiaotong University Shanghai ChinaMolecular Diagnostic Laboratory Shanghai Children's Hospital Shanghai Jiaotong University Shanghai ChinaDepartment of Neurology Shanghai Children's Hospital Shanghai Jiaotong University Shanghai ChinaDepartment of Clinical Laboratory Shanghai Children's Hospital Shanghai Jiaotong University Shanghai ChinaMolecular Diagnostic Laboratory Shanghai Children's Hospital Shanghai Jiaotong University Shanghai ChinaAbstract 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.https://doi.org/10.1002/mgg3.1499 |
| spellingShingle | Xiaojun Tang Xiaoping Lan Xiaozhen Song Wuhen Xu Yuanfeng Zhang Hong Zhang Shengnan Wu De novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent families Molecular Genetics & Genomic Medicine |
| title | De novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent families |
| title_full | De novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent families |
| title_fullStr | De novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent families |
| title_full_unstemmed | De novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent families |
| title_short | De novo variants in WDR45 underlie beta‐propeller protein‐associated neurodegeneration in five independent families |
| title_sort | de novo variants in wdr45 underlie beta propeller protein associated neurodegeneration in five independent families |
| url | https://doi.org/10.1002/mgg3.1499 |
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