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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
  1. J Andrieux1,2,
  2. C Villenet2,
  3. S Quief2,
  4. S Lignon2,
  5. S Geffroy2,
  6. C Roumier2,
  7. H de Leersnyder3,
  8. M-C de Blois3,
  9. S Manouvrier4,
  10. B Delobel5,
  11. B Benzacken6,
  12. P Bitoun7,
  13. T Attie-Bitach3,
  14. S Thomas3,
  15. S Lyonnet3,
  16. M Vekemans3,
  17. J-P Kerckaert2
  1. 1Laboratoires de Génétique Médicale, Hôpital Jeanne de Flandre, Lille, France
  2. 2Plateforme de Génomique Fonctionnelle, Université de Lille II, Lille, France
  3. 3Département de Génétique et INSERM U-393, Hôpital Necker-Enfants Malades, Paris, France
  4. 4Service de Génétique Clinique, Hôpital Jeanne de Flandre, Lille, France
  5. 5Centre de Génétique Chromosomique, Université Catholique, Lille, France
  6. 6Laboratoire de cytogénétique et Biologie de la Reproduction, Hôpital Jean Verdier, AP-HP, Bondy, France
  7. 7Génétique Médicale, Hôpital Jean Verdier, AP-HP, Bondy, France
  1. Correspondence to:
 J Andrieux
 Laboratoires de Génétique Médicale, Hôpital Jeanne de Flandre, Lille 59000, France; j-andrieux{at}chru-lille.fr

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.

Conclusion: These data support UBB as a good candidate gene for isolated cleft palate.

  • CGH, comparative genome hybridisation
  • FISH, fluorescence hybridisation
  • HMM, hidden Markov model
  • UBB, ubiquitin B
  • Smith-Magenis
  • cleft palate
  • CGH varray

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Footnotes

  • Competing interests: None declared.

  • Published Online First 11 May 2007

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