Valaparambil Karthika Ajit, Fasaludeen Alfiya, Priya Lakshmi, Menon Ramshekhar N, Menon Ramesh, Sundaram Soumya
Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, Kerala, India.
Pediatric Neurology and Neurodevelopmental Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, Kerala, India.
Indian J Pediatr. 2025 Feb;92(2):185-190. doi: 10.1007/s12098-023-04916-y. Epub 2023 Nov 9.
Chromosomal microarray is recommended as the first line of investigation in neurodevelopmental disorders (NDDs). However, advances in next-generation sequencing have unraveled more than 900 genes associated with NDDs, thus improving the genetic diagnosis. Therefore, this study was conducted to explore the utility of clinical exome sequencing (CES) in NDDs from a tertiary care centre in India. A retrospective observational analysis of 78 children with NDDs for whom CES was performed between 2017 and 2021 was conducted. The American College of Medical Genetics and Genomics (ACMG) criteria were used to classify the variants. The mean age was 5.8 ± 3.6 y, and 42 (53%) were male. Pathogenic, likely pathogenic, and variants of uncertain significance (VUS) were observed in 22 (28.2%), 10 (12.8%), and 26 (33.3%) patients, respectively, which included five copy number variants. The diagnostic yield for pathogenic and likely pathogenic variants in NDDs by CES was 41%, which was reasonably high.
染色体微阵列分析被推荐作为神经发育障碍（NDDs）的一线检测方法。然而，新一代测序技术的发展已发现900多个与NDDs相关的基因，从而提高了基因诊断水平。因此，本研究旨在探讨印度一家三级医疗中心临床外显子组测序（CES）在NDDs中的应用价值。对2017年至2021年间接受CES检测的78例NDDs患儿进行回顾性观察分析。采用美国医学遗传学与基因组学学会（ACMG）标准对变异进行分类。平均年龄为5.8±3.6岁，42例（53%）为男性。分别在22例（28.2%）、10例（12.8%）和26例（33.3%）患者中观察到致病、可能致病和意义未明的变异（VUS），其中包括5个拷贝数变异。CES对NDDs致病和可能致病变异的诊断率为41%，相当高。
