MOLECULAR SCREENING OF ADAMTSL2 GENE IN 33 PATIENTS REVEALS THE GENETIC HETEROGENEITY OF GELEOPHYSIC DYSPLASIA

Slimane Allali (1) , Carine Le Goff (1) , Isabelle Pressac-Diebold (1) , Gwendolyne Pfenning (1) , Clã©mentine Mahaut (1) , Nathalie Dagoneau (1) , Yasemin Alanay (2) , Angela F. Brady (3) , Yanick J. Crow (4) , Koen Devriendt (5) , Valérie Drouin-Garraud (6) , Elisabeth Flori (7) , David Genevieve (8) , Raoul C. Hennekam (9) , Jane A Hurst (10) , Deborah Krakow (11) , Martine Le Merrer (1) , K. D. Lichtenbelt (12) , Sally A. Lynch (13) , Stanislas Lyonnet (1) , K. Macdermot (14) , Sahar Mansour (15) , André Mégarbané (16) , Heloisa G. Santos (17) , Miranda Splitt (18) , Andrea Superti-Furga (19) , Sheila Unger (19) , Denise Williams (20) , Arnold Munnich (1) , Valerie Cormier-Daire (1)

1 Inserm U781 - Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement
2 Ankara University School of Medicine [Turkey]
3 North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
4 Genetic Medicine, University of Manchester, Manchester Academic Heath Science Centre
5 Department of Medical Genetics, Leuven University Hospital, Leuven
6 Hôpital Charles Nicolle [Rouen]
7 Department of genetics, Strasbourg hospital, Strasbourg
8 Service de Génétique Médicale
9 Department of Pediatrics, Academic Medical Center, University of Amsterdam
10 Departement of Clinical Genetics, Oxford Radcliffe Hospitals
11 Cedars-Sinai Medical Center
12 University Medical Center [Utrecht]
13 National Center for Medical Genetics, Dublin
14 North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
15 SW Thames Regional Genetics Service, St George’s University of London, London
16 USJ - Université Saint-Joseph de Beyrouth
17 Department of Medical Genetics , Lisboa
18 Institute of Human Genetics, Newcastle
19 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
20 Birmingham women's hospital, Birmingham

Geleophysic dysplasia (OMIM 231050, GD) is an autosomal recessive disorder characterized by short stature, small hands and feet, stiff joints and thick skin. Patients often present with a progressive cardiac valvular disease which can lead to an early death. In a previous study including six GD families, we have mapped the disease gene on chromosome 9q34.2 and identified mutations in the A Disintegrin And Metalloproteinase with Thrombospondin repeats-like 2 gene (ADAMTSL2). Following this study, we have collected the samples of 30 additional GD families, including 33 patients and identified ADAMTSL2 mutations in 14/33 patients, comprising 13 novel mutations. The absence of mutation in 19 patients prompted us to compare the two groups of GD patients, namely group 1, patients with ADAMTSL2 mutations (n=20, also including the 6 patients from our previous study) and group 2, patients without ADAMTSL2 mutations (n=19). We found that the main discriminating features were facial dysmorphism and tip-toe walking, almost constantly observed in group 1. No differences were found concerning heart involvement, skin thickness, recurrent respiratory and ear infections, bronchopulmonary insufficiency, laryngo-tracheal stenosis, deafness and radiographic features. We conclude that GD is a genetically heterogeneous condition. Ongoing studies will hopefully lead to the identification of another disease gene.

Mots clés: Genetics; Clinical genetics; Connective tissue disease

Slimane Allali, Carine Le Goff, Isabelle Pressac-Diebold, Gwendolyne Pfenning, Clã©mentine Mahaut, et al.. MOLECULAR SCREENING OF ADAMTSL2 GENE IN 33 PATIENTS REVEALS THE GENETIC HETEROGENEITY OF GELEOPHYSIC DYSPLASIA. Journal of Medical Genetics, 2011, 48 (6), pp.417. ⟨10.1136/jmg.2010.087544⟩. ⟨hal-00614843⟩