Genotype-phenotype correlation of 30 Smith-Magenis Syndrome patients using CGH-array: cleft palate in SMS is associated with larger deletions

Joris Andrieux ^1*, Céline Villenet ², Sabine Quief ², Sébastien Lignon ², Sandrine Geffroy ¹, Christophe Roumier ², Hélène de Leersnyder ³, Marie-Christine de Blois ³, Sylvie Manouvrier ⁴, Bruno Delobel ⁵, Brigitte Benzacken ⁶, Pierre Bitoun ⁷, Tania Attie-Bitach ³, Sophie Thomas ³, Stanislas Lyonnet ³, Michel Vekemans ³ and Jean-Pierre Kerckaert ²

¹ Laboratoires de Génétique Médicale, Hôpital Jeanne de Flandre, Lille, France
² Plateforme de Génomique fonctionnelle, Université de Lille II, Lille, France
³ Département de Génétique et INSERM U-393, Hôpital Necker-Enfants Malades,, France
⁴ Service de Génétique Clinique, Hôpital Jeanne de Flandre, Lille, France
⁵ Centre de Génétique Chromosomique, Université Catholique, Lille, France
⁶ Laboratoire de cytogénétique et Biologie de la Reproduction, Hôpital Jean Verdie, France
⁷ Génétique Médicale, Hôpital Jean Verdier, AP-HP, Bondy, France

^* To whom correspondence should be addressed. E-mail: j-andrieux{at}chru-lille.fr.

Accepted 4 April 2007

Abstract

Introduction: Smith-Magenis syndrome (SMS) is rare (prevalence 1/25.000) and associates psychomotor delay, a particular behavioral pattern and congenital anomalies. SMS is often due to less than 4 Mb chromosomal deletion at 17p11.2 locus, leading to haploinsufficiency of numerous genes. Mutations of one of them, RAI1, seems to be responsible of main criteria foud in heterozygous 17p11.2 deletion.

Materials and Methods: We studied DNA from 30 SMS patients using a 300 bp-amplimers-CGH-array encompassing 75 loci on the 22 Mb from chromosome 17 short arm.

Results: Three patients showed larger deletions (10%). Genotype-phenotype correlation revealed that two of them had cleft palate beside none of other SMS patients (p<0,007, Fisher's exact test). The smallest cleft palate SMS extra-deleted region of 1,4 Mb contains less than 16 genes and is located at 17p11.2-17p12. Among them, gene expression array data showed that Ubiquitin B precursor (UBB) is significantly expressed in first branchial arch at 4th and 5th of human development.

Conclusion: Therefore, all these data may support UBB as a good candidate gene for isolated cleft palate.

Keywords: CGH-array, Smith-Magenis, cleft palate

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Sherwood, R. J., Duren, D. L., Havill, L. M., Rogers, J., Cox, L. A., Towne, B., Mahaney, M. C. (2008). A Genomewide Linkage Scan for Quantitative Trait Loci Influencing the Craniofacial Complex in Baboons (Papio hamadryas spp.). Genetics 180: 619-628 [Abstract] [Full Text]