title: Analysis of the parental origin of de novo MECP2 mutations and X chromosome inactivation in 24 sporadic patients with Rett syndrome in China.
abstract: Rett syndrome is an X-linked neurodevelopmental disorder that predominantly affects females. It is caused by mutations in methyl-CpG-binding protein 2 gene. Due to the sex-limited expression, it has been suggested that de novo X-linked mutations may exclusively occur in male germ cells and thus only females are affected. In this study, the authors have analyzed the parental origin of mutations and the X-chromosome inactivation status in 24 sporadic patients with identified methyl-CpG-binding protein 2 gene mutations. The results showed that 22 of 24 patients have a paternal origin. Only 2 patients have a maternal origin. Except for 2 cases which were homozygotic at the androgen receptor gene locus, of the remaining 22 cases, 16 cases have a random X-chromosome inactivation pattern; the other 6 cases have a skewed X-chromosome inactivation and they favor expression of the wild allele. The relationship between X-chromosome inactivation and phenotype may need more cases to explore.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, People's Republic of China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Zhu
authors.forename: Meirong
authors.initials: M
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: Xinhua
authors.initials: X
authors.lastname: Bao
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005220:Fathers; D005260:Female; D006801:Humans; D007223:Infant; D008562:Membrane Glycoproteins; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009035:Mothers; D009154:Mutation; D010290:Parents; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017472:Receptors, Interleukin-1; D015518:Rett Syndrome / Q000235:genetics*; D049951:X Chromosome Inactivation
chemical_list: C497392:MECP2 protein, human; D008562:Membrane Glycoproteins; D051783:Methyl-CpG-Binding Protein 2; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human