Mahadevan Radha, Bhoyar Rahul C, Viswanathan Natarajan, Rajagopal Raskin Erusan, Essaki Bobby, Suroliya Varun, Chelladurai Rachel, Sankaralingam Saravanan, Shanmugam Ganesan, Vayanakkan Sriramakrishnan, Shamim Uzma, Mathur Aradhana, Jain Abhinav, Imran Mohamed, Faruq Mohammed, Scaria Vinod, Sivasubbu Sridhar, Kalyanaraman Shantaraman
Department of Neurology, Tirunelveli Medical College, Tirunelveli 627011, Tamil Nadu, India.
Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi 110025, India.
Brain Commun. 2020 Dec 19;3(1):fcaa214. doi: 10.1093/braincomms/fcaa214. eCollection 2021.
Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy is a non-progressive disorder characterized by distal tremors. Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy has been reported globally with different genetic predispositions of autosomal dominant inheritance with a high degree of penetrance. In south India, Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy has been reported in a large cohort of 48 families, in which the genetic defect was not identified. This report pertains to the whole-genome analysis of four individuals followed by repeat-primed PCR for 102 patients from a familial cohort of 325 individuals. All the patients underwent extensive clinical evaluation including neuropsychological examinations. The whole-genome sequencing was done for two affected and two unaffected individuals, belonging to two different families. The whole-genome sequencing analysis revealed the repeat expansion of TTTTA and TTTCA in intron 4 of the gene located on chromosome 8 in the patients affected with Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy, whereas the unaffected family members were negative for the similar expansion. Further, the repeat-primed PCR analysis of 102 patients showed the expansion of the TTTCA repeats in the intron 4 of gene. All patients registered for this study belong to a single community called "Nadar" whose nativity is confined to the southern districts of India, with reported unique genetic characteristics. This is the largest and most comprehensive single report on clinically and genetically characterized Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy patients belonging to a unique ethnic group worldwide.
常染色体显性遗传性皮质震颤、肌阵挛和癫痫是一种以远端震颤为特征的非进行性疾病。常染色体显性遗传性皮质震颤、肌阵挛和癫痫在全球均有报道，具有不同的常染色体显性遗传基因倾向，且外显率高。在印度南部，已有48个家族的大样本队列报道了常染色体显性遗传性皮质震颤、肌阵挛和癫痫，其中未发现基因缺陷。本报告涉及对4名个体进行全基因组分析，随后对来自325名个体的家族队列中的102名患者进行重复引物PCR。所有患者均接受了包括神经心理学检查在内的广泛临床评估。对来自两个不同家族的两名患病个体和两名未患病个体进行了全基因组测序。全基因组测序分析显示，患有常染色体显性遗传性皮质震颤、肌阵挛和癫痫的患者中，位于8号染色体上的该基因第4内含子中的TTTTA和TTTCA重复序列发生了扩增，而未患病的家庭成员未出现类似的扩增。此外,对102名患者进行的重复引物PCR分析显示该基因第4内含子中的TTTCA重复序列发生了扩增。所有登记参加本研究的患者都属于一个名为“纳达尔”的单一群体，他们的出生地仅限于印度南部地区，据报道具有独特的遗传特征。这是关于世界范围内属于独特种族群体的常染色体显性遗传性皮质震颤、肌阵挛和癫痫患者的临床和基因特征的最大且最全面的单一报告。
