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https://www.ias.ac.in/article/fulltext/jgen/099/0079

MECP2 gene; seizure; C-terminal deletion; point mutation; exon 4.

Rett syndrome (RTT) is an X-linked disorder caused by mutations in MECP2 in majority of cases. It is characterized byarrested development between 6 and 18 months of age, regression of acquired hand skills and speech, stereotypic hand movements, gaitabnormalities and seizures. There are a very few studies in India which illustrates mutation spectrum in RTT. None of the studies havecorrelated seizures with the genotype. This study describes the phenotype and genotype spectrum in children with RTT syndrome andanalyses the association of epilepsy with various clinical features and molecular findings. All children with RTT in our cohort had globaldevelopmental delay. Genetic diagnosis identified mutations of the MECP2 in all 25 children where RTT was suspected. We have identifiedpoint 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 novelinsertion variant c.337_338 (p.S113Ffs*9). All the deletions were located in the C-terminal region. Majority of the mutations (22/25) wereidentified in exon 4 which comprised of nonsense and missense types. Screening of hotspot mutations in exon 4 should be the first lineevaluation in diagnosis of RTT. Molecular testing could help in specific management of seizures in RTT.

PAYAL KAMDAR¹ MAYA THOMAS² SANGEETHA YOGANATHAN² KARTHIK MUTHUSAMY² BEENA KOSHY³ SAMUEL PHILIP OOMMEN³ REKHA AARON¹ ANITHA BARNEY¹ SUNEETHA SUSAN C. ABRAHAM¹ SUMITA DANDA¹

1. Medical Genetics, Christian Medical College, Vellore 632 004, India
2. Neurological Sciences, Christian Medical College, Vellore 632 004, India
3. Developmental Paediatrics, Christian Medical College, Vellore 632 004, India

Published

21 October 2020

Manuscript received

6 May 2020

Manuscript revised

7 July 2020

Accepted

18 August 2020