TY - JOUR T1 - Molecular screening of <em>ADAMTSL2</em> gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia JF - Journal of Medical Genetics JO - J Med Genet SP - 417 LP - 421 DO - 10.1136/jmg.2010.087544 VL - 48 IS - 6 AU - Slimane Allali AU - Carine Le Goff AU - Isabelle Pressac–Diebold AU - Gwendoline Pfennig AU - Clémentine Mahaut AU - Nathalie Dagoneau AU - Yasemin Alanay AU - Angela F Brady AU - Yanick J Crow AU - Koen Devriendt AU - Valérie Drouin-Garraud AU - Elisabeth Flori AU - David Geneviève AU - Raoul C Hennekam AU - Jane Hurst AU - Deborah Krakow AU - Martine Le Merrer AU - Klaske D Lichtenbelt AU - Sally A Lynch AU - Stanislas Lyonnet AU - Kay MacDermot AU - Sahar Mansour AU - André Megarbané AU - Heloisa G Santos AU - Miranda Splitt AU - Andrea Superti-Furga AU - Sheila Unger AU - Denise Williams AU - Arnold Munnich AU - Valérie Cormier-Daire Y1 - 2011/06/01 UR - http://jmg.bmj.com/content/48/6/417.abstract N2 - 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. ER -