Abstract
Objective
To assess yield of MECP2 gene sequence variations analysis and large deletions in suspected cases of Rett syndrome.
Design
Descriptive study.
Setting
Tertiary-care medical genetics center.
Patients
Girls with neuroregression, postnatal microcephaly and signs and symptoms suggestive of classical and atypical Rett syndrome were classified into two groups. Group I consisted of girls with Classical and atypical Rett syndrome on basis on the Revised Rett Syndrome diagnostic criteria, 2010. Group II included girls with neuroregression and postnatal microcephaly and other Rett like features but not fulfilling the above criteria.
Procedure
Sanger sequencing of coding regions and large deletional analysis of MECP2 gene.
Outcome measure
Identification of mutation in MECP2 gene.
Result
Mutation in MECP2 gene was identified in 74% (14/19) in group I and none (0/17) in group II. The mutation detection rate was 93% (13/14) in group I classical Rett syndrome girls (2 with large deletions identified with Multiplex ligation dependent probe amplification) and 20% (1/5) in group I atypical Rett syndrome girls. One novel MECP2 sequence variation was identified in group I classical Rett syndrome.
Conclusion
The yield of the mutation detection in MECP2 is higher in classical Rett syndrome. In girls with some Rett like features, but not fulfilling revised Rett syndrome diagnostic criteria, mutation testing for MECP2 gene has a low yield.
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References
Lyst MJ, Bird A. Rett syndrome: a complex disorder with simple roots. Nat Rev Genet. 2015;16:261–75.
Christodoulou J, Grimm A, Maher T, Bennetts B. RettBASE: The IRSA MECP2 Variation Database - A new mutation database in evolution. Hum Mutat. 2003; 21:466–72.
Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, et al. Rett syndrome: Revised diagnostic criteria and nomenclature. Ann Neurol. 2010;68:944–50.
Khajuria R, Gupta N, Sapra S, Gulati S, Ghosh M, Kalra V, et al. Novel non-identical MECP2 mutations in Rett syndrome family: a rare presentation. Brain Dev. 2012; 34:28–31.
Khajuria R, Gupta N, Sapra S, Gulati S, Ghosh M, Kalra V, et al. A novel MECP2 change in an Indian boy with variant Rett phenotype and congenital blindness: Implications for genetic counseling and prenatal diagnosis. J Child Neurol. 2011;26:209–13.
Das DK, Raha S, Sanghavi D, Maitra A, Udani V. Spectrum of MECP2 gene mutations in a cohort of Indian patients with Rett syndrome: report of two novel mutations. Gene. 2013;515:78–83.
Saunders CJ, Minassian BE, Chow EW, Zhao W, Vincent JB. Novel exon 1 mutations in MECP2 implicate isoform MeCP2_e1 in classical Rett syndrome. Am J Med Genet A. 2009;149A:1019–23.
Percy AK, Lane JB, Childers J, Skinner S, Annese F, Barrish J, et al. Rett syndrome: North American database. J Child Neurol. 2007;22:1338–41.
Bienvenu T, Carrié A, de Roux N, Vinet MC, Jonveaux P, Couvert P, et al. MECP2 mutations account for most cases of typical forms of Rett syndrome. Hum Mol Genet. 2000;9:1377–84.
Laurvick CL, de Klerk N, Bower C, Christodoulou J, Ravine D, Ellaway C, et al. Rett syndrome in Australia: a review of the epidemiology. J Pediatr. 2006; 148:347–52.
Olson HE, Tambunan D, LaCoursiere C, Goldenberg M, Pinsky R, Martin E, et al. Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome. Am J Med Genet A. 2015;167:2017–25.
Miltenberger-Miltenyi G, Laccone F. Mutations and polymorphisms in the human methyl CpG-binding protein MECP2. Hum Mut. 2003;22:107–15.
Francke U. Mechanisms of disease: neurogenetics of MeCP2 deficiency. Nat Clin Pract Neurol. 2006;2:212–21.
Hardwick SA, Reuter K, Williamson SL, Vasudevan V, Donald J, Slater K, et al. Delineation of large deletions of the MECP2 gene in Rett syndrome patients, including a familial case with a male proband. Eur J Hum Genet. 2007;15:1218–29.
Pan H, Li MR, Nelson P, Bao XH, Wu XR, Yu S. Large deletions of the MECP2 gene in Chinese patients with classical Rett syndrome. Clin Genet. 2006;70: 418–19.
Weaving LS, Christodoulou J, Williamson SL, Friend KL, McKenzie OL, Archer H, et al. Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. Am J Hum Genet. 2004;75:1079–93.
Ariani F, Hayek G, Rondinella D, Artuso R, Mencarelli MA, Spanhol-Rosseto A, et al. FOXG1 is responsible for the congenital variant of Rett syndrome. Am J Hum Genet. 2008;83:89–93.
Ishii T, Makita Y, Ogawa A, Amamiya S, Yamamoto M, Miyamoto A, et al. The role of different X-inactivation pattern on the variable clinical phenotype with Rett syndrome. Brain Dev. 2001;23:S161–4.
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Lallar, M., Rai, A., Srivastava, P. et al. Molecular Testing of MECP2 Gene in Rett Syndrome Phenotypes in Indian Girls. Indian Pediatr 55, 474–477 (2018). https://doi.org/10.1007/s13312-018-1336-y
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DOI: https://doi.org/10.1007/s13312-018-1336-y