title: De novo MECP2 duplication derived from paternal germ line result in dysmorphism and developmental delay.
abstract: Xq28 duplications encompassing the methyl CpG binding protein 2 (MECP2) in males exhibit a distinct phenotype, including developmental delay, facial dysmorphism, muscular hypotonia, intellectual disability, poor or absent speech, recurrent infections and early death. The vast majority of affected males inherit the MECP2 duplication from their usually asymptomatic carrier mothers. Only a few cases with Xq28 duplication originating from de novo unbalanced X/Y translocation have been reported and the paternal origin of the aberration has only been validated in three males in the related literature. Here we present a karyotypically normal male with features characteristic of the MECP2 duplication syndrome. The genome-wide SNP genotyping shows a de novo 2.26-Mb duplication from Xq28 to the terminus. The genotypes of the SNPs within the duplicated region indicated a paternal origin. Furthermore, the results of fluorescence in situ hybridization (FISH) indicated a novel Xq:Yp translocation, characterized as der(Y)t(Y;X)(p11.32;q28), which suggests an aberrant that occurred during spermatogenesis. The phenotype is compared to the previously reported cases with Xq28 duplication originated from an unbalanced X/Y translocation, and there was no specific part of the phenotype that could be contributed to the origin of parental imbalances. This report further highlights the capacity of high-molecular cytogenetic methods, such as SNP array and FISH, in the identification of submicroscopic rearrangement, structural configuration and parental origin of aberrant while in the evaluation of children with idiopathic developmental delay and intellectual disability.
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
authors.forename: Dar-Shong
authors.initials: DS
authors.lastname: Lin
authors.forename: Tzu-Po
authors.initials: TP
authors.lastname: Chuang
authors.forename: Ming-Fu
authors.initials: MF
authors.lastname: Chiang
authors.forename: Che-Sheng
authors.initials: CS
authors.lastname: Ho
authors.forename: Chung-Der
authors.initials: CD
authors.lastname: Hsiao
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Huang
authors.forename: Tsu-Yen
authors.initials: TY
authors.lastname: Wu
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Tsai-Chuan
authors.initials: TC
authors.lastname: Chen
authors.forename: Ling-Hui
authors.initials: LH
authors.lastname: Li
mesh_terms: D002648:Child; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D002658:Developmental Disabilities / Q000235:genetics*; D018392:Genomic Imprinting; D005854:Germ Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: CGH; CNVs; Disomy; FISH; FoSTeS; Fork Stalling and Template Switching; IFN-α; MECP2; MECP2 duplication; SNP; SNP array; Translocation; Xq28; comparative genome hybridization; copy number variations; fluorescence in situ hybridization; interferon alpha; methyl CpG binding protein 2; single-nucleotide polymorphism