Rett syndrome (RTT) is an X-linked dominant neurodevelopment disorder, which is mainly caused by gene mutation of methyl-CpG-binding protein 2 (MECP2). The correlations between genotype, X chromosome inactivation (XCI), and phenotype have been studied, but the results are conflicting. In the present study, XCI patterns in patients and their mothers, parental origin of skewed X chromosome in patients, and the correlations between XCI, genotype, and phenotype were analyzed in 52 cases of RTT with MECP2 mutations, 50 RTT mothers, and 48 normal female controls. The results showed XCI and genotype had limitations in explaining all the phenotypic manifestations of RTT. Other genomic factors have to be considered to explain the phenotypic differences.
Amir RE, Van den Veyver IB, Wan M., et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet.1999 ;23:185-188.
2.
Hoffbuhr K., Devaney JM, LaFleur B., et al. MeCP2 mutations in children with and without the phenotype of Rett syndrome. Neurol.2001;56:1486-1495.
3.
Weaving LS, Williamson SL, Bennetts B., et al. Effects of MECP2 mutation type, location and X-inactivation in modulating Rett syndrome phenotype. Am J Med Genet.2003;118A:103-114.
4.
Amir RE, Van den Veyver IB, Schultz R., et al. Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes. Ann Neurol.2000 ;47:670-679.
5.
Schanen C., Houwink EJF, Dorrani N., et al. Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome. Am J Med Genet.2004 ;126A:129-140.
6.
Nielson JB, Henriksen KF, Hansen C., et al. MECP2 mutations in Danish patients with Rett syndrome: high frequency of mutations but no consistent correlations with clinical severity or with the X chromosome inactivation pattern. Eur J Hum Genet.2001;9:178-184.
7.
Ishii T., Makita Y., Ogawa A., et al. The role of different X-inactivation pattern on the variable clinical phenotype with Rett syndrome. Brain Dev.2001;23:S161-S164.
8.
Huppke P., Maier EM, Warnke A., et al. Very mild cases of Rett syndrome with skewed X inactivation . J Med Genet.2006;43(10): 814-816.
9.
Wan M., Lee SSJ, Zhang X., et al. Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet.1999;65:1520-1529.
10.
Knudsen GP, Neilson TCS, Pedersen J., et al. Increased skewing X chromosome inactivation in Rett syndrome patients and their mothers. Eur J Hum Genet.2006;14(11):1189-1194.
11.
Fukuda T., Yamashita Y., Nagamitsu S., et al. Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms. Brain Dev.2005;27:211-217.
12.
Pan H., Wang YP, Bao XH, et al. MECP2 gene mutation analysis in Chinese patients with Rett syndrome . Eur J Hum Genet.2002;10:484-486.
13.
Allen RC, Zoghbi HY, Moseley AB, et al. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen receptor gene correlates with X chromosome inactivation . Am J Hum Genet.1992;51:1229-1239.
14.
Archer HL, Whatley SD, Evans JC, et al. Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients. J Med Genet.2006;43:451-456.
15.
Krepischi ACV , Kok F., Otto PGX chromosome-inactivation patterns in patients with Rett syndrome. Hum Genet.1998; 102:310-321.
16.
Yurov YB, Vorsanova SG, Kolotii AD, et al. Molecular-cytogenetic investigation of skewed chromosome X inactivation in Rett syndrome. Brain Dev.2001;23:S214-S217.
17.
Zoghbi HY, Percy AK, Schultz RJ, et al. Patterns of X chromosome inactivation in the Rett syndrome. Brain Dev.1990;12:131-135.
18.
Auranen M., Vanhala R., Vosman M., et al. MECP2 gene analysis in classical Rett syndrome and in patients with Rett-like features. Neurol.2001;56:611-617.
19.
Camus P., Abbadi N., Perrier MC, et al. X chromosome inactivation in 30 girls with Rett syndrome: analysis using the prob. Hum Genet.1996;97:247-250.
20.
Webb T., Watkiss E.A comparative study of X-inactivation in Rett syndrome probands and control subjects. Clin Genet.1996;49:189-195.
21.
Trappe R., Laccone F., Cobilanschi J., et al. MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin. Am J Hum Genet.2001;68:1093-1101.
22.
Girard M., Couvert P., Carrie A., et al. Parental origin of de novo MECP2 mutation in Rett syndrome. Eur J Hum Genet.2001;9:231-236.
23.
Kerr AM, Archer HL, Evans JC, et al. People with MECP2 mutation-positive Rett disorder who converse . J Intellect Disabil Res. 2006;50:386-394.
24.
Nielsen JB, Ravn K., Schwartz M.A 77-year-old woman and a preserved speech variant among the Danish Rett patients with mutations in MECP2. Brain Dev.2001;23(suppl):S230-S230.
