Shan Lin1, Jia-Bin Zeng1, Gui-Xian Zhao2, Zhen-Zhen Yang1, Hui-Ping Huang1, Min-Ting Lin1, Zhi-Ying Wu3, Ning Wang4, Wan-Jin Chen4, Ling Fang5. 1. Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China. 2. Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China. 3. Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Medical Neurobiology of Zhejiang Province, Hangzhou, China. 4. Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Molecular Neurology, Fuzhou, China. 5. Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Molecular Neurology, Fuzhou, China. Electronic address: paulinefz@126.com.
Abstract
PURPOSE: Tuberous sclerosis complex (TSC) is characterized by the development of hamartomas in multiple organ systems. This study attempted to screen mutations and to investigate the mutation distribution and related phenotypes including epilepsy of Chinese TSC patients. METHODS: We performed the genotypic analysis of TSC1 and TSC2 genes in 77 unrelated Chinese TSC patients using direct Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA). RESULTS: Mutations were identified in a total of 63 (81.8%) cases, including 18 TSC1 mutations (8 nonsense mutations, 6 frameshift, 1 in-frame shift, 1 missense and 2 splice-site) and 45 TSC2 mutations (13 missense, 3 nonsense, 6 splicing, 6 in-frame shift,12 frameshift mutations and 5 large deletions). Large deletions were presented exclusively in TSC2 gene, accounting for 7.9% of all mutations in this study. Fourteen novel mutations were identified in this study. CONCLUSIONS: Epilepsy occurs in approximately 75.3% (58/77) of patients. Hypomelanotic macules occurred significantly more often in patients with TSC2 mutations and cases with TSC1/TSC2 mutations had a significantly higher frequency of cortical nodule than patients with no mutations identified. Overall, our data expands the spectrum of mutations associated with the TSC loci and will be of value to the genetic counseling in patients with the disease.
PURPOSE:Tuberous sclerosis complex (TSC) is characterized by the development of hamartomas in multiple organ systems. This study attempted to screen mutations and to investigate the mutation distribution and related phenotypes including epilepsy of Chinese TSCpatients. METHODS: We performed the genotypic analysis of TSC1 and TSC2 genes in 77 unrelated Chinese TSCpatients using direct Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA). RESULTS: Mutations were identified in a total of 63 (81.8%) cases, including 18 TSC1 mutations (8 nonsense mutations, 6 frameshift, 1 in-frame shift, 1 missense and 2 splice-site) and 45 TSC2 mutations (13 missense, 3 nonsense, 6 splicing, 6 in-frame shift,12 frameshift mutations and 5 large deletions). Large deletions were presented exclusively in TSC2 gene, accounting for 7.9% of all mutations in this study. Fourteen novel mutations were identified in this study. CONCLUSIONS:Epilepsy occurs in approximately 75.3% (58/77) of patients. Hypomelanotic macules occurred significantly more often in patients with TSC2 mutations and cases with TSC1/TSC2 mutations had a significantly higher frequency of cortical nodule than patients with no mutations identified. Overall, our data expands the spectrum of mutations associated with the TSC loci and will be of value to the genetic counseling in patients with the disease.
Authors: Sultan Abdulwadoud Alshoabi; Abdullgabbar M Hamid; Fahad H Alhazmi; Abdulaziz A Qurashi; Osamah M Abdulaal; Khaled M Aloufi; Tareef S Daqqaq Journal: Quant Imaging Med Surg Date: 2022-01
Authors: Jessica Robinson; Orhan Uzun; Ne Ron Loh; Isabelle Rose Harris; Thomas E Woolley; Adrian J Harwood; Jennifer Frances Gardner; Yasir Ahmed Syed Journal: BMC Med Date: 2022-04-20 Impact factor: 11.150