Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia. Issue 6 (17th March 2011)

• Record Type: Journal Article
• Authors: Allali, Slimane; Le Goff, Carine; Pressac–Diebold, Isabelle; Pfennig, Gwendoline; Mahaut, Clémentine; Dagoneau, Nathalie; Alanay, Yasemin; Brady, Angela F; Crow, Yanick J; Devriendt, Koen; Drouin-Garraud, Valérie; Flori, Elisabeth; Geneviève, David; Hennekam, Raoul C; Hurst, Jane; Krakow, Deborah; Le Merrer, Martine; Lichtenbelt, Klaske D; Lynch, Sally A; Lyonnet, Stanislas; MacDermot, Kay; Mansour, Sahar; Megarbané, André; Santos, Heloisa G; Splitt, Miranda; Superti-Furga, Andrea; Unger, Sheila; Williams, Denise; Munnich, Arnold; Cormier-Daire, Valérie
• Is Part Of: Journal of medical genetics. Volume 48:Issue 6(2011)
• Page Start: 417
• Page End: 421
• Publication Date: 2011-03-17
• Subjects: Geleophysic dysplasia -- ADAMTSL2 -- cardiac valvular disease -- genetics -- clinical genetics, connective tissue disease; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2010.087544
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Geleophysic dysplasia (GD, OMIM 231050) is an autosomal recessive disorder characterised 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 ). Methods: 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). Results: The main discriminating features were facial dysmorphism and tip-toe walking, which were 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. Conclusions: It is concluded that GD is a genetically heterogeneous condition. Ongoing studies will hopefully lead to the identification of another disease gene.