Identification of a novel <i>TSC1</i> gene variant in a patient with atypical vitiligo-like skin lesions: Unveiling the hidden tuberous sclerosis complex

作者全名："Liu, Linli; Wang, Yanbo; Zhang, Zhengzhong; Yu, Chunshui; Chen, Jin"

作者地址："[Liu, Linli; Chen, Jin] Chongqing Med Univ, Dept Dermatol, First Affiliated Hosp, Chongqing, Peoples R China; [Liu, Linli; Yu, Chunshui] Suining Cent Hosp, Dept Dermatol, Suining, Sichuan, Peoples R China; [Wang, Yanbo] Langzhong Peoples Hosp, Dept Dermatol, Nanchong, Sichuan, Peoples R China; [Zhang, Zhengzhong] Affiliated Hosp, North Sichuan Med Coll, Dept Dermatol, Nanchong, Sichuan, Peoples R China; [Chen, Jin] Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Chen, J (通讯作者)，Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：MOLECULAR GENETICS & GENOMIC MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001179188800001

JCR分区：Q3

影响因子：2

年份：2024

卷号：12

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：minigene assay; splicing variant; TSC1; tuberous sclerosis complex

摘要："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."

基金机构：National Natural Science Foundation of China

基金资助正文："We would like to thank the patient, his family, and the physicians who contributed to this study."