title: The incidence of hypoplasia of the corpus callosum in patients with dup (X)(q28) involving MECP2 is associated with the location of distal breakpoints.
abstract: Duplications of Xq28 harboring the methyl CpG binding protein 2 (MECP2) gene explain approximately 1% of X-linked intellectual disability (XLID). The common clinical features observed in patients with dup(X)(q28) are severe ID, infantile hypotonia, mild dysmorphic features and a history of recurrent infections, and MECP2 duplication syndrome is now recognized as a clinical entity. While some patients with this syndrome have other characteristic phenotypes, the reason for the spectrum of phenotypes has not been clarified. Since dup(X)(q28) rearrangements vary in size and location, genes other than MECP2 might affect the phenotype. We used a high-density oligonucleotide array to carry out precise mapping in eight Japanese families in which dup(X)(q28) was detected using an in-house bacterial artificial chromosome-based microarray to screen cohorts of individuals with multiple congenital anomalies and intellectual disability (MCA/ID) or with XLID. We hypothesized that the size, gene content, and location of dup(X)(q28) may contribute to variable expressively observed in MECP2 duplication syndrome. Genotype-phenotype correlation in our cases together with cases reported in the literature suggested that copy-number gains between two low copy repeats (LCRK1 and LCRL1) are associated with the incidence of hypoplasia of the corpus callosum. Further studies are necessary to understand the mechanism of this association.
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Honda
authors.forename: Shin
authors.initials: S
authors.lastname: Hayashi
authors.forename: Takaya
authors.initials: T
authors.lastname: Nakane
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Mizuno
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshihashi
authors.forename: Takeo
authors.initials: T
authors.lastname: Kubota
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakagawa
authors.forename: Yu-Ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D061085:Agenesis of Corpus Callosum / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D000483:Alleles; D019457:Chromosome Breakage; D056905:Chromosome Breakpoints; D058674:Chromosome Duplication; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D059906:Neuroimaging; D010375:Pedigree; D049951:X Chromosome Inactivation
chemical_list: D051783:Methyl-CpG-Binding Protein 2