Sudarshan Shruthi, Kumar Atin, Gupta Arun, Bhari Neetu, Sethuraman Gomathy, Kaushal Tanuja, Pradhan Ankita, Sapra Savita, Gupta Neerja, Kaur Punit, Gulati Sheffali, Chakrawarty Biswaroop, Danda Sumita, Bhatt Meenakshi, Kapoor Seema, Girisha Katta M, Sankhyan Naveen, Kabra Madhulika, Chowdhury Madhumita Roy
Department of Pediatrics, Division of Genetics, All India Institute of Medical Sciences, New Delhi, India.
Department of Radio Diagnosis, All India Institute of Medical Sciences, New Delhi, India.
J Pediatr Genet. 2020 Sep 7;10(4):274-283. doi: 10.1055/s-0040-1716495. eCollection 2021 Dec.
Tuberous sclerosis complex (TSC) is a multiorgan disorder characterized by formation of hamartomas and broad phenotypic spectrum including seizures, mental retardation, renal dysfunction, skin manifestations and brain tubers. It is inherited in an autosomal dominant pattern, caused due to mutation in either or genes. Seizures are one of the major presenting symptoms of TSC that helps in early diagnosis. The present study describes the mutation spectrum in and genes in TSC patients and their association with neurocognitive-behavioral phenotypes. Ninety-eight TSC patients were enrolled for TSC genetic testing after detailed clinical and neurobehavioral assessment. Large genomic rearrangement testing was performed by multiplex ligation-dependent probe amplification (MLPA) technique for all cases and Sanger sequencing was performed for MLPA negative cases. Large rearrangements were identified in approximately 1% in and 14.3% in genes. The present study observed the presence of duplications in two (2%) cases, both involving contiguous genes which to the best of our knowledge is reported for the first time. 8.1% of small variants were identified in the gene and 85.7% in gene, out of which 23 were novel variations and no variants were found in six (6.1%) cases. This study provides a representative picture of the distribution of variants in the and genes in Indian population along with the detailed assessment of neurological symptoms. This is the largest cohort study from India providing an overview of comprehensive clinical and molecular spectrum.
结节性硬化症（TSC）是一种多器官疾病，其特征是错构瘤的形成以及广泛的表型谱，包括癫痫发作、智力迟钝、肾功能障碍、皮肤表现和脑结节。它以常染色体显性模式遗传，由TSC1或TSC2基因的突变引起。癫痫发作是TSC的主要症状之一，有助于早期诊断。本研究描述了TSC患者中TSC1和TSC2基因的突变谱及其与神经认知行为表型的关联。在进行详细的临床和神经行为评估后，98例TSC患者被纳入TSC基因检测。所有病例均采用多重连接依赖探针扩增（MLPA）技术进行大基因组重排检测，MLPA阴性病例进行桑格测序。在TSC1基因中约1%的病例和TSC2基因中14.3%的病例中发现了大的重排。本研究在两例（2%）病例中观察到重复的存在，两者均涉及相邻基因，据我们所知，这是首次报道。在TSC1基因中鉴定出8.1%的小变异，在TSC2基因中鉴定出85.7%的小变异，其中23个是新变异，6例（6.1%）未发现变异。本研究提供了印度人群中TSC1和TSC2基因变异分布的代表性情况以及对神经症状的详细评估。这是来自印度的最大队列研究，提供了全面的临床和分子谱概述。
