Rett syndrome (RTT) is an X-linked disorder caused by mutations in MECP2 in majority of cases. It is characterized by arrested development between 6 and 18 months of age, regression of acquired hand skills and speech, stereotypic hand movements, gait abnormalities and seizures. There are a very few studies in India which illustrates mutation spectrum in RTT. None of the studies have correlated seizures with the genotype. This study describes the phenotype and genotype spectrum in children with RTT syndrome and analyses the association of epilepsy with various clinical features and molecular findings. All children with RTT in our cohort had global developmental delay. Genetic diagnosis identified mutations of the MECP2 in all 25 children where RTT was suspected. We have identified point mutations in 20 patients, one insertion and four deletions by Sanger sequencing, namely c.1164_1207 (44 bp), c.1165_1207 (43 bp), c.1157_1197 (41 bp) del and c.1157_1188 (32 bp). Clinically, none of the patients with deletion had seizures. We identified one novel insertion variant c.337_338 (p.S113Ffs*9). All the deletions were located in the C-terminal region. Majority of the mutations (22/25) were identified in exon 4 which comprised of nonsense and missense types. Screening of hotspot mutations in exon 4 should be the first line evaluation in diagnosis of RTT. Molecular testing could help in specific management of seizures in RTT.

中文翻译：

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甲基 CpG 结合蛋白 2 基因突变及其与癫痫的关联：来自印度次大陆的单中心研究

在大多数情况下，雷特综合征 (RTT) 是由 MECP2 突变引起的 X 连锁疾病。它的特点是在 6 至 18 个月大时发育停滞、获得的手部技能和言语退化、刻板的手部运动、步态异常和癫痫发作。印度很少有研究说明 RTT 中的突变谱。没有一项研究将癫痫发作与基因型相关联。本研究描述了 RTT 综合征儿童的表型和基因型谱，并分析了癫痫与各种临床特征和分子发现的关联。我们队列中所有患有 RTT 的儿童都有整体发育迟缓。遗传诊断在所有 25 名怀疑 RTT 的儿童中确定了 MECP2 的突变。我们已经确定了 20 名患者的点突变，通过 Sanger 测序得到 1 个插入和 4 个缺失，即 c.1164_1207 (44 bp)、c.1165_1207 (43 bp)、c.1157_1197 (41 bp) del 和 c.1157_1188 (32 bp)。临床上，缺失的患者均未出现癫痫发作。我们鉴定了一种新的插入变体 c.337_338 (p.S113Ffs*9)。所有的缺失都位于 C 端区域。大多数突变 (22/25) 在由无义和错义类型组成的外显子 4 中鉴定。外显子 4 热点突变的筛查应该是 RTT 诊断的一线评估。分子检测有助于 RTT 癫痫发作的具体管理。所有的缺失都位于 C 端区域。大多数突变 (22/25) 在由无义和错义类型组成的外显子 4 中鉴定。外显子 4 热点突变的筛查应该是 RTT 诊断的一线评估。分子检测有助于 RTT 癫痫发作的具体管理。所有的缺失都位于 C 端区域。大多数突变 (22/25) 在由无义和错义类型组成的外显子 4 中鉴定。外显子 4 热点突变的筛查应该是 RTT 诊断的一线评估。分子检测有助于 RTT 癫痫发作的具体管理。