Identification of a novel TSC1 gene variant in a patient with atypical vitiligo‐like skin lesions: Unveiling the hidden tuberous sclerosis complex
Abstract Background Tuberous sclerosis complex (TSC), an autosomal‐dominant disorder, is characterized by hamartomas affecting multiple organ systems. The underlying etiology of TSC is the pathogenic variations of the TSC1 or TSC2 genes. The phenotype variability of TSC could lead to missed diagnosi...
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.2403 |
| _version_ | 1827307614481940480 |
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| author | Linli Liu Yanbo Wang Zhengzhong Zhang Chunshui Yu Jin Chen |
| author_facet | Linli Liu Yanbo Wang Zhengzhong Zhang Chunshui Yu Jin Chen |
| author_sort | Linli Liu |
| collection | DOAJ |
| description | Abstract Background Tuberous sclerosis complex (TSC), an autosomal‐dominant disorder, is characterized by hamartomas affecting multiple organ systems. The underlying etiology of TSC is the pathogenic variations of the TSC1 or TSC2 genes. The phenotype variability of TSC could lead to missed diagnosis; therefore, the latest molecular diagnostic criteria for identifying a heterozygous pathogenic variant in either the TSC1 or TSC2 gene filled this gap. Furthermore, the pathogenicity of numerous variants remains unverified, potentially leading to misinterpretations of their functional consequences. Methods In this study, a single patient presenting with atypical vitiligo‐like skin lesions suspected to have TSC was enrolled. Targeted next‐generation sequencing and Sanger sequencing were employed to identify a pathogenic variant. Additionally, a minigene splicing assay was conducted to assess the impact of TSC1 c.1030‐2A>T, located in intron 10, on RNA splicing. Results A novel TSC1: c.1030‐2A>T heterozygosis variant was identified in intron 10. In vitro minigene assay revealed that the c.1030‐2A>T variant caused exon 11 skipping, resulting in a frameshift in the absence of 112 base pairs of mature messenger RNA and premature termination after 174 base pairs (p.Ala344Glnfs*59). Conclusion The detection of this novel pathogenic TSC1 variant in the patient with atypical vitiligo‐like skin lesions enrolled in our study ultimately resulted in the diagnosis of TSC. As a result, our study contributes to expanding the mutational spectrum of the TSC1 gene and refining the genotype–phenotype map of TSC. |
| first_indexed | 2024-04-24T18:42:19Z |
| format | Article |
| id | doaj.art-b1ed055b64db4f04bb247c055ec3062c |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-24T18:42:19Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-b1ed055b64db4f04bb247c055ec3062c2024-03-27T10:47:28ZengWileyMolecular Genetics & Genomic Medicine2324-92692024-03-01123n/an/a10.1002/mgg3.2403Identification of a novel TSC1 gene variant in a patient with atypical vitiligo‐like skin lesions: Unveiling the hidden tuberous sclerosis complexLinli Liu0Yanbo Wang1Zhengzhong Zhang2Chunshui Yu3Jin Chen4Department of Dermatology The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Dermatology Langzhong People's Hospital Nanchong Sichuan ChinaDepartment of Dermatology Affiliated Hospital of North Sichuan Medical College Nanchong Sichuan ChinaDepartment of Dermatology Suining Central Hospital Suining Sichuan ChinaDepartment of Dermatology The First Affiliated Hospital of Chongqing Medical University Chongqing ChinaAbstract Background Tuberous sclerosis complex (TSC), an autosomal‐dominant disorder, is characterized by hamartomas affecting multiple organ systems. The underlying etiology of TSC is the pathogenic variations of the TSC1 or TSC2 genes. The phenotype variability of TSC could lead to missed diagnosis; therefore, the latest molecular diagnostic criteria for identifying a heterozygous pathogenic variant in either the TSC1 or TSC2 gene filled this gap. Furthermore, the pathogenicity of numerous variants remains unverified, potentially leading to misinterpretations of their functional consequences. Methods In this study, a single patient presenting with atypical vitiligo‐like skin lesions suspected to have TSC was enrolled. Targeted next‐generation sequencing and Sanger sequencing were employed to identify a pathogenic variant. Additionally, a minigene splicing assay was conducted to assess the impact of TSC1 c.1030‐2A>T, located in intron 10, on RNA splicing. Results A novel TSC1: c.1030‐2A>T heterozygosis variant was identified in intron 10. In vitro minigene assay revealed that the c.1030‐2A>T variant caused exon 11 skipping, resulting in a frameshift in the absence of 112 base pairs of mature messenger RNA and premature termination after 174 base pairs (p.Ala344Glnfs*59). Conclusion The detection of this novel pathogenic TSC1 variant in the patient with atypical vitiligo‐like skin lesions enrolled in our study ultimately resulted in the diagnosis of TSC. As a result, our study contributes to expanding the mutational spectrum of the TSC1 gene and refining the genotype–phenotype map of TSC.https://doi.org/10.1002/mgg3.2403minigene assaysplicing variantTSC1tuberous sclerosis complex |
| spellingShingle | Linli Liu Yanbo Wang Zhengzhong Zhang Chunshui Yu Jin Chen Identification of a novel TSC1 gene variant in a patient with atypical vitiligo‐like skin lesions: Unveiling the hidden tuberous sclerosis complex Molecular Genetics & Genomic Medicine minigene assay splicing variant TSC1 tuberous sclerosis complex |
| title | Identification of a novel TSC1 gene variant in a patient with atypical vitiligo‐like skin lesions: Unveiling the hidden tuberous sclerosis complex |
| title_full | Identification of a novel TSC1 gene variant in a patient with atypical vitiligo‐like skin lesions: Unveiling the hidden tuberous sclerosis complex |
| title_fullStr | Identification of a novel TSC1 gene variant in a patient with atypical vitiligo‐like skin lesions: Unveiling the hidden tuberous sclerosis complex |
| title_full_unstemmed | Identification of a novel TSC1 gene variant in a patient with atypical vitiligo‐like skin lesions: Unveiling the hidden tuberous sclerosis complex |
| title_short | Identification of a novel TSC1 gene variant in a patient with atypical vitiligo‐like skin lesions: Unveiling the hidden tuberous sclerosis complex |
| title_sort | identification of a novel tsc1 gene variant in a patient with atypical vitiligo like skin lesions unveiling the hidden tuberous sclerosis complex |
| topic | minigene assay splicing variant TSC1 tuberous sclerosis complex |
| url | https://doi.org/10.1002/mgg3.2403 |
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