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Khajuria et al. J Transl Genet Genom 2020;4:91-103 Journal of Translational
DOI: 10.20517/jtgg.2020.06 Genetics and Genomics

Original Article Open Access

Spectrum of MECP2 mutations in Indian females
with Rett Syndrome - a large cohort study

Rajni Khajuria , Neerja Gupta , Kees E. P. van Roozendaal , Savita Sapra , Manju Ghosh , Sheffali Gulati ,
2
1
1
3,6
1
1
Eric E. J. Smeets 3,4,6 , Leopold M. G. Curfs 3,4,5,6 , Madhulika Kabra 1
1 Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India.
2 Division of Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India.
3 Department of Clinical Genetics, Maastricht University Medical Centre, P.O. Box 5800, Maastricht 6202 AZ, The Netherlands.
4 Governor Kremers Center, Maastricht University Medical Centre, P.O. Box 5800, Maastricht 6202 AZ, The Netherlands.
5 School for Public Health and Primary Care CAPHRI, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands.
6 School for Oncology and Developmental Biology GROW, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The
Netherlands.
Correspondence to: Prof. Madhulika Kabra, Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences,
New Delhi 110029, India. E-mail: madhulikakabra@hotmail.com
How to cite this article: Khajuria R, Gupta N, van Roozendaal KEP, Sapra S, Ghosh M, Gulati S, Smeets EEJ, Curfs LMG, Kabra M.
Spectrum of MECP2 mutations in Indian females with Rett Syndrome - a large cohort study. J Transl Genet Genom 2020;4:91-103.
http://dx.doi.org/10.20517/jtgg.2020.06

Received: 31 Jan 2020 First Decision: 20 Mar 2020 Revised: 15 Apr 2020 Accepted: 23 Apr 2020 Available online: 16 May 2020

Science Editor: Tjitske Kleefstra Copy Editor: Jing-Wen Zhang Production Editor: Jing Yu

Abstract
Aim: This study aimed to characterize MECP2 gene variants in Indian female patients with classical Rett syndrome
(RTT).

Methods: Seventy-two patients fulfilling the revised diagnostic criteria of classical RTT were enrolled and exons 2-4
of MECP2 gene were analyzed by Sanger sequencing followed by quantitative analysis using MLPA. Bioinformatic
analysis was done using different software packages to predict the effect of sequence variations on the function of
the MeCP2 protein.

Results: A heterogeneous spectrum of MECP2 sequence variants including 13 novel variants was identified with
a detection rate of 98.6%. The majority of the variants were distributed in the functional domain of MECP2
with most missense variants clustered in methyl binding domain and truncating variants in interdomain and
transcription repression domain of MECP2. Genotype-phenotype correlations revealed that patients carrying early
truncating variants presented with a more severe phenotype.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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