Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia

  • J Med Genet. 2011 Jun;48(6):417-21. doi: 10.1136/jmg.2010.087544.
Slimane Allali  1 ,  Carine Le Goff ,  Isabelle Pressac-Diebold ,  Gwendoline Pfennig ,  Clémentine Mahaut ,  Nathalie Dagoneau ,  Yasemin Alanay ,  Angela F Brady ,  Yanick J Crow ,  Koen Devriendt ,  Valérie Drouin-Garraud ,  Elisabeth Flori ,  David Geneviève ,  Raoul C Hennekam ,  Jane Hurst ,  Deborah Krakow ,  Martine Le Merrer ,  Klaske D Lichtenbelt ,  Sally A Lynch ,  Stanislas Lyonnet ,  Kay MacDermot ,  Sahar Mansour ,  André Megarbané ,  Heloisa G Santos ,  Miranda Splitt ,  Andrea Superti-Furga ,  Sheila Unger ,  Denise Williams ,  Arnold Munnich ,  Valérie Cormier-Daire
Affiliations
  • 1. Department of Genetics, INSERM U781, Université Paris Descartes, Hôpital Necker, Paris, France.
PMID: 21415077 DOI: 10.1136/jmg.2010.087544
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.