Clinical feature and Genetics in Rett syndrome; A report on Iranian patients
Iranian Journal of Child Neurology,
Vol. 13 No. 4 (2019),
1 Mehr 2019
,
Page 37-51
https://doi.org/10.22037/ijcn.v13i4.17554
Abstract
Background: Rett Syndrome is characterized by normal development for the first 6–18 months of life followed by the loss of fine and gross motor skills and the ability to engage in social interaction. Mutations methyl CpG-binding protein 2 gene (MECP2) have been found in the majority of patients. This study was performed to investigate the relation of Rett clinical diagnosis and its relation with mutations in MECP2. Materials and Methods: children suspected to Rett syndrome were invited to take part in this study. Those who had met classic Rett syndrome diagnostic criteria were enrolled. Severity of symptoms was assessed for all patients. Of peripheral blood samples collected in EDTA tubes, the genomic DNA was extracted by standard salting out method. MEPC2 gene mutation was studied by DNA sequencing method. Results and conclusion: 23 patients accepted to participate in the study. 11(47.8%) patients had MECP2 gene mutation meanwhile 12 ones (52.2%) had no mutation. change in genetics was in association with phenotypical manifestations. The most prevalent mutation was p.v288 which is mostly in association with partially or uncontrolled seizures. This was the first time that Rett syndrome patients were studied in both clinical manifestations and genetic changes in Iran.
- Rett Syndrome
- MECP2
- Gene mutation
- Phenotype
How to Cite
References
Rett A. On a unusual brain atrophy syndrome in hyperammonemia in childhood. Wien Med Wochenschr 1996;116(37):723-6.
Percy A. The American History of Rett Syndrome.Pediatr Neurol 2014;50(1):1-3.
Medline Plus. (2012). Rett syndrome. Retrieved May 10, 2012, from http://www.nlm.nih.gov/medlineplus/ency/article/001536.htm
Amir RE, Van-den-Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999;23:185–8.
Van den Veyver IB, Zoghbi HY. Genetic basis of Rett syndrome. Ment Retard Dev Disabil Res Rev 2002;8(2):82-6.
Moretti P, Zoghbi HY. MeCP2 dysfunction in Rett syndrome and related disorders. Curr Opin Genet Dev 2006;16:276–81.
Nan X, Bird A. The biological functions of the methyl-CpG-binding protein MeCP2 and its implication in Rett syndrome. Brain Dev 2001;Suppl 1:S32-7.
Wakefield RI, Smith BO, Nan X, Free A, Soteriou A, Uhrin D, et al. The solution structure of the domain from MeCP2 that binds to methylated DNA. J Mol Biol 1999;291(5):1055–65.
Percy AK, Lane JB, Childers J, Skinner S, Annese F, Barrish J. Rett syndrome: North American database. J Child Neurol 2007;22:1338–41.
Tao J, Van Esch H, Hagedorn-Greiwe M. Mutations in theX-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) geneare associated with severe neurodevelopmental retardation. Am J Hum Genet 2004;75:1149– 54.
Weaving LS, Christodoulou J, Williamson SL, Friend KL, McKenzie OL, Archer H. Mutations ofCDKL5 cause a severe neurodevelopmental disorder with infantilespasms and mental retardation. Am J Hum Genet 2004;75:1079– 93.
Evans JC, Archer HL, Colley JP, Ravn K, Nielsen JB, Kerr A. Early onset seizures and Rettlikefeatures associated with mutations in CDKL5. Eur J Hum Genet 2005;13:1113-20.
Scala E, Ariani F, Mari F. CDKL5/STK9 is mutated in Rettsyndrome variant with infantile spasms. J Med Genet 2005;2005;13:1113-20.
Scala E, Ariani F, Mari F, Caselli R, Pescucci C, Longo I. Disruption of Netrin G1 by abalanced chromosome translocation in a girl with Rettsyndrome. Eur J Hum Genet 2005;13:921-27.
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.
Wan M, Lee SSJ, Zhang X, Houwink-Manville I, Song HR, Amir RE. Rett syndrome and beyond: Recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet 1999;65:1520-29.
Monrós E, Armstrong J, Aibar E, Poo P, Canós I, Pineda M. Rett syndrome in Spain: mutation analysis and clinical correlations. Brain Dev 2001;Suppl 1:S251-3.
Amano K, Nomura Y, Segawa M, Yamakawa K. Mutational analysis of the MECP2 gene in Japanese patients with Rett syndrome. J Hum Genet 2000;45(4):231-6.
Lee S, Wan M, Francke U. Spectrum of MECP2 mutations in Rett syndrome. . Brain & Development 2001;23:S138–S43.
Cooper DN, Youssoufian H. The CpG dinucleotide and human genetic disease. Hum Genet 1988;78(2):151-5.
Adkins NL, Georgel PT. MeCP2: structure and function. Biochem Cell Biol 2011;89:1-11.
Amir RE, Van den Veyver I, Schultz R, Malicki DM, Tran CQ, Dahle EJ. Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes. Ann Neurol 2000;47:670-9.
Cheadle J, Gill H, Fleming N, Maynard J, Kerr A, Leonard H, et al. Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location. Hum Mol Genet 2000;9:1119–29.
Lam CW, Yeung WL, Ko CH, Poon PM, Tong SF, Chan KY, et al. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J Med Genet 2000;37(12):1377-1384.
Hoffbuhr K, Devaney JM, LaFleur B, Sirianni N, Scacheri C, Giron J, et al. MeCP2 mutations in children with and without the phenotype of Rett syndrome. Neurology 2001;56(11):1486-95.
Huppke P, Laccone F, Krämer N, Engel W, Hanefeld F. Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients. Hum Mol Genet 2000;9(9):1369-75.
Hampson K, Woods CG, Latif F, Webb T. Mutations in the MECP2 gene in a cohort of girls with Rett syndrome. J Med Genet 2000;37(8):610-2.
Bourdon V, Philippe C, Labrune O, Amsallem D, Arnould C, Jonveaux P. A detailed analysis of the MECP2 gene: prevalence of recurrent mutations and gross DNA rearrangements in Rett syndrome patients. Hum Genet 2001;108(1):43-50.
Trappe R, Laccone F, Cobilanschi J, Meins M, Huppke P, Hanefeld F, et al. MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin. Am J Hum Genet 2001;68(5):1093-101.
.Auranen M, Vanhala R, Vosman M, Levander M, Varilo T, Hietala M, et al. MECP2 gene analysis in classical Rett syndrome and in patients with Rett-like features. Neurology 2001;56(5):611-7.
De Bona C, Zappella M, Hayek G, Meloni I, Vitelli F, Bruttini M, et al. Preserved speech variant is allelic of classic Rett syndrome. Eur J Hum Genet 2000;8(5):325-30.
Orrico A, Lam C, Galli L, Dotti MT, Hayek G, Tong SF, et al. MECP2 mutation in male patients with non-specific X-linked mental retardation. FEBS Lett 2000;481(3):285-8.
Ellaway CJ, Badawi N, Raffaele L, Christodoulou J, Leonard H. A case of multiple congenital anomalies in association with Rett syndrome confirmed by MECP2 mutation screening. Clin Dysmorphol 2001;10(3):185-8.
CCHMC Molecular Genetics Laboratory Mutation Database; https://research.cchmc.org/LOVD2/variants.php?select_db=MECP2&action=view&view=0000402%2C0000111%2C0 [database on the Internet]2018.
Huppke P, Held M, Hanefeld F, Engel W, Laccone . Influence of mutation type and location on phenotype in 123 patients with Rett syndrome. Neuropediatrics 2002;33(2):63-8.
Yamada Y, Miura K, Kumagai T, Hayakawa C, Miyazaki S, Matsumoto A, et al. Molecular analysis of Japanese patients with Rett syndrome: Identification of five novel mutations and genotype-phenotype correlation. Hum Mutat 2001;18(3):18-253.
Philippe C, Villard L, De Roux N, Raynaud M, Bonnefond JP, Pasquier L, et al. Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update. Eur J Med Genet 2006;49(1):9-18.
Bienvenu T, Villard L, De Roux N, Bourdon V, Fontes M, Beldjord C, et al. Spectrum of MECP2 mutations in Rett syndrome. Genet Test 2002;6(1):1-6.
Lima FT, Brunoni D, Schwartzman JS, Pozzi MC, Kok F, Juliano Y, et al. Genotype-phenotype correlation in Brazillian Rett syndrome patients. Arq Neuropsiquiatr 2009;67(3A):577-84.
Raizis AM, Saleem M, MacKay R, George PM. Spectrum of MECP2 mutations in New Zealand Rett syndrome patients. N Z Med J 2009;122(1296):21-8.
Psoni S, Sofocleous C, Traeger-Synodinos J, Kitsiou-Tzeli S, Kanavakis E, Fryssira-Kanioura H. MECP2 mutations and clinical correlations in Greek children with Rett syndrome and associated neurodevelopmental disorders. Brain Dev 2012;34(6):487-95.
Obata K, Matsuishi T, Yamashita Y, Fukuda T, Kuwajima K, Horiuchi I, et al. Mutation analysis of the methyl-CpG binding protein 2 gene (MECP2) in patients with Rett syndrome. J Med Genet 2000;37(8):608-10.
Buyse IM, Fang P, Hoon KT, Amir RE, Zoghbi HY, Roa BB. Diagnostic testing for Rett syndrome by DHPLC and direct sequencing analysis of the MECP2 gene: identification of several novel mutations and polymorphisms. Am J Hum Genet 2000;67(6):1428-36.
Zappella M, Meloni I, Longo I, Hayek G, Renieri A. Preserved speech variants of the Rett syndrome: molecular and clinical analysis. Am J Med Genet 2001;104(1):14-22.
Erlandson A, Hallberg B, Hagberg B, Wahlström J, Martinsson T. MECP2 mutation screening in Swedish classical Rett syndrome females. Eur Child Adolesc Psychiatry 2001;10(2):117-21.
Laccone F, Huppke P, Hanefeld F, Meins M. Mutation spectrum in patients with Rett syndrome in the German population: Evidence of hot spot regions. Hum Mutat 2001;17(3):183-90.
Nicolao P, Carella M, Giometto B, Tavolato B, Cattin R, Govannucci-Uzielli ML, et al. DHPLC analysis of the MECP2 gene in Italian Rett patients. Hum Mutat 2001;18(2):132-40.
Vacca M, Filippini F, Budillon A, Rossi V, Mercadante G, Manzati E, et al. Mutation analysis of the MECP2 gene in British and Italian Rett syndrome females. J Mol Med (Berl) 2001;78(1):648-55.
Schanen C, Houwink EJ, Dorrani N, Lane J, Everett R, Feng A, et al. Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome. Am J Med Genet A 2004;126A(2):129-40.
Masuyama T, Matsuo M, Jing JJ, Tabara Y, Kitsuki K, Yamagata H, et al. Classic Rett syndrome in a boy with R133C mutation of MECP2. Brain Dev 2005;27(6):439-42.
Kappella M, Meloni I, Longo I, Canitano R, Hayek G, Rosaia L, et al. Study of MECP2 gene in Rett syndrome variants and autistic girls. Am J Med Genet B Neuropsychiatr Genet 2003;119B(1):102-7.
Kleefstra T, Yntema HG, Nillesen WM, Oudakker AR, Mullaart RA, Geerdink N, et al. MECP2 analysis in mentally retarded patients: implications for routine DNA diagnostics. Eur J Hum Genet 2004;12(1):24-8.
Matijević T, Knezević J, Barisić I, Resić B, Culić V, Pavelić J. The MECP2 gene mutation screening in Rett syndrome patients from Croatia. Ann N Y Acad Sci 2006;1091:225-32.
Zahorakova D, Rosipal R, Hadac J, Zumrova A, Bzduch V, Misovicova N, et al. Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms. J Hum Genet 2007;52(4):342-8.
Kim HJ, Kim SH, Kim HD, Lee JS, Lee YM, Koo KY, et al. Genetic and epileptic features in Rett syndrome. Yonsei Med J 2012;53(3):495-500.
Chae JH, Hwang H, Hwang YS, Cheong HJ, Kim KJ. Influence of MECP2 gene mutation and X-chromosome inactivation on the Rett syndrome phenotype. J Child Neurol 2004;19(7):503-8.
Xiang F, Stenbom Y, Anvret M. MECP2 mutations in Swedish Rett syndrome clusters. Clin Genet 2002;61(5):384-5.
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