title: What does the nature of the MECP2 mutation tell us about parental origin and recurrence risk in Rett syndrome?
abstract: The MECP2 mutations occurring in the severe neurological disorder Rett syndrome are predominantly de novo, with rare familial cases. The aims of this study were to provide a precise estimate of the parental origin of MECP2 mutations using a large Chinese sample and to assess whether parental origin varied by mutation type. The parental origin was paternal in 84/88 [95.5%, (95% confidence interval 88.77-98.75)] of sporadic Chinese cases. However, in a pooled sample including data from the literature the spectrum of mutations occurring on maternally and paternally derived chromosomes differed significantly. The excess we found of 'single base pair gains or losses' on maternally derived MECP2 gene alleles suggests that this mutational category is associated with an elevated risk of gonadal mosaicism, which has implications for genetic counseling.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Bao
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.forename: L
authors.initials: L
authors.lastname: Jia
authors.forename: H
authors.initials: H
authors.lastname: Pan
authors.forename: S
authors.initials: S
authors.lastname: Fehr
authors.forename: M
authors.initials: M
authors.lastname: Davis
authors.forename: H
authors.initials: H
authors.lastname: Leonard
authors.forename: D
authors.initials: D
authors.lastname: Ravine
authors.forename: X
authors.initials: X
authors.lastname: Wu
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015518:Rett Syndrome / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012737:Sex Factors
chemical_list: D017931:DNA Primers; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2