title: Genotype phenotype correlation of 30 patients with Smith-Magenis syndrome (SMS) using comparative genome hybridisation array: cleft palate in SMS is associated with larger deletions.
abstract: BACKGROUND
  Smith-Magenis syndrome (SMS) is rare (prevalence 1 in 25 000) and is associated with psychomotor delay, a particular behavioural pattern and congenital anomalies. SMS is often due to a chromosomal deletion of <4 Mb at the 17p11.2 locus, leading to haploinsufficiency of numerous genes. Mutations of one of these gemes, RAI1, seems to be responsible for the main features found with heterozygous 17p11.2 deletions.
  
  
  METHODS
  We studied DNA from 30 patients with SMS using a 300 bp amplimers comparative genome hybridisation array encompassing 75 loci from a 22 Mb section from the short arm of chromosome 17.
  
  
  RESULTS
  Three patients had large deletions (10%). Genotype-phenotype correlation showed that two of them had cleft palate, which was not found in any of the other patients with SMS (p<0.007, Fisher's exact test). The smallest extra-deleted region associated with cleft palate in SMS is 1.4 Mb, contains <16 genes and is located at 17p11.2-17p12. Gene expression array data showed that the ubiquitin B precursor (UBB) is significantly expressed in the first branchial arch in the fourth and fifth weeks of human development.
  
  
  CONCLUSIONS
  These data support UBB as a good candidate gene for isolated cleft palate.
authors.forename: J
authors.initials: J
authors.lastname: Andrieux
authors.forename: C
authors.initials: C
authors.lastname: Villenet
authors.forename: S
authors.initials: S
authors.lastname: Quief
authors.forename: S
authors.initials: S
authors.lastname: Lignon
authors.forename: S
authors.initials: S
authors.lastname: Geffroy
authors.forename: C
authors.initials: C
authors.lastname: Roumier
authors.forename: H
authors.initials: H
authors.lastname: de Leersnyder
authors.forename: M-C
authors.initials: MC
authors.lastname: de Blois
authors.forename: S
authors.initials: S
authors.lastname: Manouvrier
authors.forename: B
authors.initials: B
authors.lastname: Delobel
authors.forename: B
authors.initials: B
authors.lastname: Benzacken
authors.forename: P
authors.initials: P
authors.lastname: Bitoun
authors.forename: T
authors.initials: T
authors.lastname: Attie-Bitach
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.forename: M
authors.initials: M
authors.lastname: Vekemans
authors.forename: J-P
authors.initials: JP
authors.lastname: Kerckaert
mesh_terms: D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D002972:Cleft Palate / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D001523:Mental Disorders / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D017384:Sequence Deletion; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C431552:RAI1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors