title: Deletion of chromosome 21 disturbs human brain morphogenesis.
abstract: OBJECTIVE
  Humans with small deletions of chromosome 21 provide important models for understanding the role of dosage-sensitive genes in brain morphogenesis. To identify chromosome 21 genes responsible for defects of the central nervous system, we determined the deleted regions and brain malformations in three unrelated individuals with overlapping partial deletions of chromosome 21.
  
  
  METHODS
  Fluorescent in situ hybridization and magnetic resonance imaging were used to define the chromosomal structure and structural brain abnormalities present in these three individuals.
  
  
  RESULTS
  The regions of chromosome 21 found to be deleted in these individuals were as follows: case 1: KCNJ6 to the telomere; case 2: ITSN1 to the telomere; and case 3: ITSN1 to PCNT2. The abnormalities of brain structure shared by all included microcephaly, pachygyria, polymicrogyria, colpocephaly, hypoplastic corpus callosum and white matter, hypoplastic cerebellum, and enlarged ventricular system. The clinical features in common included mental retardation, microcephaly, facial dysmorphism, and epilepsy (severe in one patient).
  
  
  CONCLUSIONS
  From analyses of the molecular, cytogenetic, and neuroimaging data from these three individuals, combined with those from previously reported cases, we infer that deletion of an 8.4-Mb region in chromosome band 21q22.2-22.3 (KCNJ6-COL6A2) is associated with cortical dysplasia. We propose that one or more dosage-sensitive genes in this region contributes to cortical development and that deletion of 21q22.2-22.3 should be considered in the diagnosis of mentally retarded patients with facial dysmorphism and cerebral dysplasia.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Cedars-Sinai Health System and Department of Human Genetics, University of California at Los Angeles, CA, USA.
authors.forename: Guimei
authors.initials: G
authors.lastname: Yao
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Chen
authors.forename: Laura
authors.initials: L
authors.lastname: Flores-Sarnat
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Barlow
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Palka
authors.forename: John B
authors.initials: JB
authors.lastname: Moeschler
authors.forename: Barbara
authors.initials: B
authors.lastname: McGillivray
authors.forename: Richard P
authors.initials: RP
authors.lastname: Morse
authors.forename: Julie R
authors.initials: JR
authors.lastname: Korenberg
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D001921:Brain / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000196:embryology; D002675:Child, Preschool; D002872:Chromosome Deletion; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D038081:Organogenesis / Q000235:genetics*; D011859:Radiography