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Variant Profile of MECP2 Gene in Sri Lankan Patients with Rett Syndrome

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Abstract

Rett syndrome (RTT) is a rare monogenic disorder affecting 1 in 10,000 live female births causing severe neurodegenerative symptoms. We analyzed the molecular genetic variants in the gene encoding the methyl-CpG binding protein 2 (MECP2) of 16 girls with RTT. Their mutation profile was as follows; Already described variants: p.R168X in 25% (n = 4), p.T158M in 25% (n = 4), p.R255X in 12.5% (n = 2), p.R133C in 12.5% (n = 2), p.R294X in 6.25% (n = 1), p.K177X in 6.25% (n = 1). Novel variants: a large deletion (c.868_1188del321) in 6.25% (n = 1) and a p.X499L in 6.25% (n = 1). We also looked at the genotype to phenotype correlation of these variants. Most of the mutations were C>T in CpG hot spot as seen in other populations.

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Data Availability

Availability of data and materials—all data is published in the manuscript material is available with the authors. We, however, can’t provide personal information or data containing identification of patients in any form.

Abbreviations

RTT:

Rett syndrome

MECP2:

Methyl‐CpG‐binding protein 2

MBD:

Methyl-CpG binding domain

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Acknowledgments

The authors wish to thank the laboratory staff the referring physicians and clinical geneticists. Special thanks to Dr. P.D. Ratnayake, Neurology Unit, Lady Ridgeway Hospital, Colombo, Sri Lanka and Dr. S.M.A. Jayawardena, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka. Authors wish to thank the laboratory staff of the Asiri Sugical Hospital and the Human Genetics Unit faculty of Medicine University of Colombo and the referring physicians.

Funding

There was no funding for this study.

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Authors and Affiliations

  1. Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka

    D. Hettiarachchi, N. F. Neththikumara, B. A. P. S. Pathirana & V. H. W. Dissanayake

  2. Department of Anatomy and Human Genetics, Faculty of Medicine, University of Colombo, No. 25, Kynsey Road, Colombo, 00800, Sri Lanka

    D. Hettiarachchi

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  1. D. Hettiarachchi
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  2. N. F. Neththikumara
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  3. B. A. P. S. Pathirana
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Contributions

DH wrote the first draft of the manuscript with contributions from all. All authors reviewed, modified and approved the final version of the manuscript. NFN and BAPSP performed the analysis. VHWD designed and guided the study.

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Correspondence to D. Hettiarachchi.

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All authors declare that they have no competing interests.

Ethics Approval

Ethics approval was obtained by the ERC of The Faculty of Medicine University of Colombo to study rare genetic conditions in the Sri Lankan population. The procedure was part of the patient’s care and posed no additional risk to the patients’ health. No identifiable information of the study participants is disclosed. All procedures performed in studies involving human participants were by the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Hettiarachchi, D., Neththikumara, N.F., Pathirana, B.A.P.S. et al. Variant Profile of MECP2 Gene in Sri Lankan Patients with Rett Syndrome. J Autism Dev Disord 50, 118–126 (2020). https://doi.org/10.1007/s10803-019-04230-7

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