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| Auteurs principaux: | , , , , , |
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| Format: | Artículo Open Access |
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Wiley
2025
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| Accès en ligne: | https://onlinelibrary.wiley.com/doi/10.1002/cns.70708 |
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| _version_ | 1867009894869106688 |
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| author | Yi Zhang Hui‐Fen Huang Juan‐Juan Xie Wang Ni Hao Yu Zhi‐Ying Wu |
| author_facet | Yi Zhang Hui‐Fen Huang Juan‐Juan Xie Wang Ni Hao Yu Zhi‐Ying Wu Yi Zhang Hui‐Fen Huang Juan‐Juan Xie Wang Ni Hao Yu Zhi‐Ying Wu |
| collection | Wiley Open Access |
| contents | Genetic and Clinical Characteristics of Chinese Adult Patients With Krabbe Disease Yi Zhang Hui‐Fen Huang Juan‐Juan Xie Wang Ni Hao Yu Zhi‐Ying Wu CNS Neuroscience & Therapeutics ABSTRACT Aim This study aims to expand the clinical and genetic spectrum of Krabbe disease (KD) in Chinese adult patients and to improve diagnosis and understanding of its phenotypic diversity. Methods Patients clinically suspected of leukodystrophy were recruited between 2015 and 2025. Clinical features were collected, and whole‐exome sequencing (WES) was performed to identify potential variants. The pathogenicity of detected variants was classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Functional assays assessing protein expression, processing, secretion, subcellular localization, and enzymatic activity were conducted to further validate variant pathogenicity. Results Fourteen unrelated patients were genetically diagnosed with KD, and their genetic and clinical features were summarized. Eleven variants in GALC were identified, including a novel missense variant c.1019C>T (p.P340L) which is not reported in the Human Gene Mutation Database (HGMD). Unlike most adult patients who typically present with spastic paraplegia, the patient carrying this variant exhibited initial symptoms of peripheral neuropathy. Functional experiments demonstrated that the variant led to impaired protein processing and localization, as well as reduced GALC enzymatic activity. Other variants including p.D56H, p.L377X, p.L441X, and p.L634S also affected GALC functions to varying degrees. Conclusion This study enhances the genotypic and phenotypic characterization of KD in China, aiding in differential diagnosis and genetic counseling. Functional data reinforce the pathogenicity of identified variants. 10.1002/cns.70708 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/cns.70708 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_cns_70708 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Genetic and Clinical Characteristics of Chinese Adult Patients With Krabbe Disease Yi Zhang Hui‐Fen Huang Juan‐Juan Xie Wang Ni Hao Yu Zhi‐Ying Wu CNS Neuroscience & Therapeutics Genetic and Clinical Characteristics of Chinese Adult Patients With Krabbe Disease Yi Zhang Hui‐Fen Huang Juan‐Juan Xie Wang Ni Hao Yu Zhi‐Ying Wu CNS Neuroscience & Therapeutics ABSTRACT Aim This study aims to expand the clinical and genetic spectrum of Krabbe disease (KD) in Chinese adult patients and to improve diagnosis and understanding of its phenotypic diversity. Methods Patients clinically suspected of leukodystrophy were recruited between 2015 and 2025. Clinical features were collected, and whole‐exome sequencing (WES) was performed to identify potential variants. The pathogenicity of detected variants was classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Functional assays assessing protein expression, processing, secretion, subcellular localization, and enzymatic activity were conducted to further validate variant pathogenicity. Results Fourteen unrelated patients were genetically diagnosed with KD, and their genetic and clinical features were summarized. Eleven variants in GALC were identified, including a novel missense variant c.1019C>T (p.P340L) which is not reported in the Human Gene Mutation Database (HGMD). Unlike most adult patients who typically present with spastic paraplegia, the patient carrying this variant exhibited initial symptoms of peripheral neuropathy. Functional experiments demonstrated that the variant led to impaired protein processing and localization, as well as reduced GALC enzymatic activity. Other variants including p.D56H, p.L377X, p.L441X, and p.L634S also affected GALC functions to varying degrees. Conclusion This study enhances the genotypic and phenotypic characterization of KD in China, aiding in differential diagnosis and genetic counseling. Functional data reinforce the pathogenicity of identified variants. 10.1002/cns.70708 http://creativecommons.org/licenses/by/4.0/ |
| title | Genetic and Clinical Characteristics of Chinese Adult Patients With Krabbe Disease |
| topic | CNS Neuroscience & Therapeutics |
| url | https://onlinelibrary.wiley.com/doi/10.1002/cns.70708 |