title: A sibship with duplication of Xq28 inherited from the mother; genomic characterization and clinical outcomes.
abstract: Loss-of-function mutations in methyl-CpG-binding protein 2 (MECP2; MIM *300005) results in the Rett syndrome, whereas gain-of-function mutations are associated with the MECP2 duplication syndrome.
  
  
  
  We did research on a family with two brothers showing Xq28 duplication syndrome using various molecular cytogenetic techniques such as multiplex ligation-dependent probe amplification and array-based genomic hybridization.
  
  
  
  The duplicated region had several genes including MECP2 and interleukin-1 receptor associated kinase 1 (IRAK1; MIM *300283). MECP2 and IRAK1 were associated with the neurological phenotypes in dose-sensitive and dose-critical manner. The brothers demonstrated severe intellectual disability, autistic features, generalized hypotonia, recurrent infections, epilepsy, choreiform movements such as hand-wringing movement, and moderate increased spasticity with the lower limbs. The X-inactivation test showed a complete skewed X inactivation pattern of mother. In this reason, the mother had the same loci duplication but showed significantly little neurological manifestation compared to the two sons.
  
  
  
  MECP2/IRAK1 duplication at Xq28 is inherited as an X-linked recessive trait and male-specific disorder associated with severe intellectual disability. We tried to analyze the information of the relationship between neuropsychiatric phenotype and the extent of duplication at Xq28 by comparing with previous reports.
authors.affiliation: Department of Pediatrics, CHA Bundang Medical Center, School of Medicine, CHA University, 351 Yatap-dong, Bundang-gu, Seongnam, 463-712, Republic of Korea.
authors.forename: Dong Keon
authors.initials: DK
authors.lastname: Yon
authors.affiliation: Genetics Laboratory, Fertility Center, CHA Gangnam Medical Center, School of Medicine, CHA University, 606-13 Yeoksam-dong, Gangnam-gu, Seoul, 06135, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: GenoLifeCare Division, BioCore, Seoul, Republic of Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Genetics Laboratory, Fertility Center, CHA Gangnam Medical Center, School of Medicine, CHA University, 606-13 Yeoksam-dong, Gangnam-gu, Seoul, 06135, Republic of Korea. shshim@cha.ac.kr.|Department of Biomedical Science, College of Life Science, CHA University, 335 Pankyo-ro, Bundang-gu, Seongnam, 13488, Republic of Korea. shshim@cha.ac.kr.
authors.forename: Sung Han
authors.initials: SH
authors.lastname: Shim
authors.affiliation: Department of Pediatrics, CHA Bundang Medical Center, School of Medicine, CHA University, 351 Yatap-dong, Bundang-gu, Seongnam, 463-712, Republic of Korea. barnabas@cha.ac.kr.
authors.forename: Kyu Young
authors.initials: KY
authors.lastname: Chae
mesh_terms: D000328:Adult; D002648:Child; D058674:Chromosome Duplication; D041321:Chromosomes, Human, X / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics*; D008297:Male; D000072741:Maternal Inheritance; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics*; D049951:X Chromosome Inactivation
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: IRAK1; MECP2; MECP2 duplication syndrome; Xq28 duplication