title: A systematic analysis of small supernumerary marker chromosomes using array CGH exposes unexpected complexity.
abstract: OBJECTIVE
  A small supernumerary marker chromosome is often seen in patients with developmental disorders. Prior to array-based comparative genomic hybridization markers were rarely genotyped end to end. In this study, a valid genotype-to-phenotype correlation was possible because the supernumerary marker chromosomes were fully characterized by array-based comparative genomic hybridization in a genome-wide analysis.
  
  
  METHODS
  Ten consecutive de novo small supernumerary marker chromosome cases were systematically genotyped using G-banding, C-banding, AgNOR staining, whole-genome array-based comparative genomic hybridization, and fluorescence in situ hybridization.
  
  
  RESULTS
  Among 10 small supernumerary marker chromosome cases studied, 4 (40%) were not identified by array-based comparative genomic hybridization because of low-level mosaicism or because they lacked euchromatin. One case (10%) was a simple pericentromeric marker extending from 5p13.3 to 5q11.2. Five (50%) markers showed unexpected complexity. Two cases had markers that were derivative acrocentric (AgNOR+) chromosomes with the euchromatin from chromosomes 18p or 19p. Each of the other three cases with complex markers had unusual characteristics including a marker from noncontiguous segments of chromosome 19q, a highly complex rearrangement involving a chromosome 20 homolog as well as the small supernumerary marker chromosome, and a mosaic duplication of a proximal 8p marker.
  
  
  CONCLUSIONS
  Small supernumerary marker chromosomes are frequently complex on the basis of our small sample. Whole-genome array-based comparative genomic hybridization characterization of the small supernumerary marker chromosome provided informed genetic counseling.
authors.affiliation: Medical Genetics and Genomics Laboratory, Kaiser Permanente Southern California, Los Angeles, California, USA. kavita.reddy@gmail.com
authors.forename: Kavita S
authors.initials: KS
authors.lastname: Reddy
authors.forename: Swaroop
authors.initials: S
authors.lastname: Aradhya
authors.forename: Jeanne
authors.initials: J
authors.lastname: Meck
authors.forename: George
authors.initials: G
authors.lastname: Tiller
authors.forename: Sridevi
authors.initials: S
authors.lastname: Abboy
authors.forename: Harold
authors.initials: H
authors.lastname: Bass
mesh_terms: D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009030:Mosaicism; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers