Sharma Shivani, Govindaraj Periyasamy, Chickabasaviah Yasha T, Siram Ramesh, Shroti Akhilesh, Seshagiri Doniparthi V, Debnath Monojit, Bindu Parayil S, Taly Arun B, Nagappa Madhu
Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India.
Laboratory of Human Molecular Genetics, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, Telangana, India.
Ann Indian Acad Neurol. 2022 May-Jun;25(3):407-416. doi: 10.4103/aian.aian_269_22. Epub 2022 Jun 14.
Charcot-Marie-Tooth (CMT) disease is the commonest inherited neuromuscular disorder and has heterogeneous manifestations. Data regarding genetic basis of CMT from India is limited. This study aims to report the variations by using high throughput sequencing in Indian CMT cohort.
Fifty-five probands (M:F 29:26) with suspected inherited neuropathy underwent genetic testing (whole exome: 31, clinical exome: 17 and targeted panel: 7). Their clinical and genetic data were analysed.
Age at onset ranged from infancy to 54 years. Clinical features included early-onset neuropathy (=23), skeletal deformities (=45), impaired vision (=8), impaired hearing (=6), facial palsy (=8), thickened nerves (=4), impaired cognition (=5), seizures (=5), pyramidal signs (=7), ataxia (=8) and vocal cord palsy, slow tongue movements and psychosis in one patient each. Twenty-eight patients had demyelinating electrophysiology. Abnormal visual and auditory evoked potentials were noted in 60.60% and 37.5% respectively. Sixty two variants were identified in 37 genes including variants of uncertain significance (=34) and novel variants (=45). Eleven patients had additional variations in genes implicated in CMTs/ other neurological disorders. Ten patients did not have variations in neuropathy associated genes, but had variations in genes implicated in other neurological disorders. In seven patients, no variations were detected.
In this single centre cohort study from India, genetic diagnosis could be established in 87% of patients with inherited neuropathy. The identified spectrum of genetic variations adds to the pool of existing data and provides a platform for validation studies in cell culture or animal model systems.
夏科-马里-图斯（CMT）病是最常见的遗传性神经肌肉疾病，临床表现具有异质性。来自印度的关于CMT遗传基础的数据有限。本研究旨在通过高通量测序报告印度CMT队列中的变异情况。
55例疑似遗传性神经病的先证者（男∶女为29∶26）接受了基因检测（全外显子组检测：31例，临床外显子组检测：17例，靶向基因panel检测：7例）。对他们的临床和基因数据进行了分析。
发病年龄从婴儿期到54岁不等。临床特征包括早发性神经病（=23例）、骨骼畸形（=45例）、视力受损（=8例）、听力受损（=6例）、面瘫（=8例）、神经增粗（=4例）、认知障碍（=5例）、癫痫发作（=5例）、锥体束征（=7例）、共济失调（=8例）以及1例患者出现声带麻痹、1例患者出现舌运动缓慢和1例患者出现精神病症状。28例患者有脱髓鞘电生理表现。视觉和听觉诱发电位异常分别在60.60%和37.5%的患者中被发现。在37个基因中鉴定出62个变异，包括意义未明的变异（=34个）和新变异（=45个）。11例患者在与CMT/其他神经系统疾病相关的基因中有额外变异。10例患者在神经病相关基因中没有变异，但在与其他神经系统疾病相关的基因中有变异。7例患者未检测到变异。
在这项来自印度的单中心队列研究中，87%的遗传性神经病患者能够建立基因诊断。所鉴定的遗传变异谱丰富了现有数据，并为细胞培养或动物模型系统中的验证研究提供了一个平台。
