TY - JOUR
T1 - Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia
AU - Allali, Slimane
AU - Le Goff, Carine
AU - Pressace-Diebold, Isabelle
AU - Pfennig, Gwendoline
AU - Mahaut, Clémentine
AU - Dagoneau, Nathalie
AU - Alanay, Yasemin
AU - Brady, Angela F.
AU - Crow, Yanick J.
AU - Devriendt, Koen
AU - Drouin-Garraud, Valérie
AU - Flori, Elisabeth
AU - Geneviève, David
AU - Hennekam, Raoul C.
AU - Hurst, Jane
AU - Krakow, Deborah
AU - Le Merrer, Martine
AU - Lichtenbelt, Klaske D.
AU - Lynch, Sally A.
AU - Lyonnet, Stanislas
AU - MacDermot, Kay
AU - Mansour, Sahar
AU - Megarbané, André
AU - Santos, Heloisa G.
AU - Splitt, Miranda
AU - Superti-Furga, Andrea
AU - Unger, Sheila
AU - Williams, Denise
AU - Munnich, Arnold
AU - Cormier-Daire, Valérie
PY - 2011/6
Y1 - 2011/6
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.
AB - 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.
U2 - 10.1136/jmg.2010.087544
DO - 10.1136/jmg.2010.087544
M3 - Article
C2 - 21415077
SN - 1468-6244
VL - 48
SP - 417
EP - 421
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 6
ER -