Eser Metin, Hekimoglu Gulam, Kutlubay Busra, Sager Safiye Gunes, Turkyilmaz Ayberk
Department of Medical Genetics, Umraniye Education and Research Hospital, University of Health Sciences, Istanbul, Turkey.
Department of Histology and Embryology, Hamidiye International Faculty of Medicine, University of Health Sciences, Istanbul, Turkey.
Mol Genet Genomics. 2024 Dec 26;300(1):6. doi: 10.1007/s00438-024-02210-w.
Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by the formation of benign tumors in various organs, particularly in the central nervous system. We aimed to delineate the molecular profile of Turkish individuals diagnosed with TSC by analyzing the TSC1 and TSC2 genes using next-generation sequencing (NGS). Sophia Genetics' Sophia Inherited Disease Panel was used to perform NGS on 22 individuals diagnosed with TSC and to identify pathogenic variants in the TSC1 and TSC2 genes. Among the 22 cases, mutations were found in 3 (13.6%) for TSC1 and in 16 (73%) for TSC2, while 3 (13.6%) exhibited no detectable mutations. Notably, one individual with a TSC2 mutation presented with angiofibroma, ungual fibroma, and pitted dental enamel, while another had cardiac rhabdomyoma. Autism spectrum disorders were observed in 6 (27%) with TSC2 mutations, including one with autistic behavior. Abnormal motor development was noted in 3 (13.6%), of which 2 had TSC2 mutations. Severe intellectual disability was found in 3 (13.6%) with TSC2 mutations, and developmental delay was seen in 2 (9%) with TSC2 mutations. Epileptic encephalopathy occurred in 3 (13.6%), with 2 having TSC2 mutations. Additionally, 6 (27%) exhibited drug resistance for focal seizures, with 5 of them having TSC2 mutations. These findings are consistent with other research indicating that TSC2 mutations are associated with a more severe phenotypic range compared to TSC1 mutations. Moreover, our analysis showed that some people with TSC1/TSC2 mutations did not match diagnostic criteria. This highlights the importance of genetic testing and molecular profiling in understanding the clinical variability and aiding in the management of TSC patients.
结节性硬化症（TSC）是一种罕见的遗传性疾病，其特征是在各个器官，尤其是中枢神经系统中形成良性肿瘤。我们旨在通过使用下一代测序（NGS）分析TSC1和TSC2基因，来描绘诊断为TSC的土耳其个体的分子图谱。使用索菲亚遗传学公司的索菲亚遗传性疾病检测板对22名诊断为TSC的个体进行NGS，以鉴定TSC1和TSC2基因中的致病变异。在这22例病例中，TSC1基因有3例（13.6%）发生突变，TSC2基因有16例（73%）发生突变，而3例（13.6%）未检测到突变。值得注意的是，一名患有TSC2突变的个体出现了血管纤维瘤、甲周纤维瘤和凹痕状牙釉质，而另一名患有心脏横纹肌瘤。在6例（27%）TSC2突变患者中观察到自闭症谱系障碍，其中1例有自闭症行为。3例（13.6%）出现运动发育异常，其中2例有TSC2突变。3例（13.6%）TSC2突变患者存在严重智力残疾，2例（9%）TSC2突变患者出现发育迟缓。3例（13.6%）发生癫痫性脑病，其中2例有TSC2突变。此外，6例（27%）对局灶性癫痫发作表现出耐药性，其中5例有TSC2突变。这些发现与其他研究一致，表明与TSC1突变相比，TSC2突变与更严重的表型范围相关。此外，我们的分析表明，一些TSC1/TSC2突变患者不符合诊断标准。这凸显了基因检测和分子图谱分析在理解临床变异性以及辅助TSC患者管理方面的重要性。
