title: Subtle chromosomal rearrangements in children with unexplained mental retardation.
abstract: BACKGROUND
  No explanation for moderate to severe mental retardation is apparent in about 40% of cases. Although small chromosomal rearrangements may account for some undiagnosed cases, a lack of genome-wide screening methods has made it impossible to ascertain the frequency of such abnormalities.
  
  
  METHODS
  A fluorescence in-situ hybridisation (FISH) test was used to examine the integrity of chromosome ends in 284 children with unexplained moderate to severe retardation, and in 182 children with unexplained mild retardation. 75 normal men were also tested. When a chromosomal rearrangement was found, its size was estimated, and members of the child's family were investigated.
  
  
  RESULTS
  Subtle chromosomal abnormalities occurred with a frequency of 7.4% in the children with moderate to severe mental retardation, and of 0.5% in the children with mild retardation. The abnormalities had an estimated population prevalence of 2.1 per 10,000, and were familial in almost half of cases.
  
  
  CONCLUSIONS
  Once recognisable syndromes have been excluded, abnormalities that include the ends of chromosomes are the commonest cause of mental retardation in children with undiagnosed moderate to severe mental retardation. Owing to the high prevalence of familial cases, screening for subtle chromosomal rearrangements is warranted in children with unexplained moderate to severe mental retardation.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Knight
authors.forename: R
authors.initials: R
authors.lastname: Regan
authors.forename: A
authors.initials: A
authors.lastname: Nicod
authors.forename: S W
authors.initials: SW
authors.lastname: Horsley
authors.forename: L
authors.initials: L
authors.lastname: Kearney
authors.forename: T
authors.initials: T
authors.lastname: Homfray
authors.forename: R M
authors.initials: RM
authors.lastname: Winter
authors.forename: P
authors.initials: P
authors.lastname: Bolton
authors.forename: J
authors.initials: J
authors.lastname: Flint
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D019465:Craniofacial Abnormalities / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D010375:Pedigree