2. Academic Validation
  3. Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia

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

Affiliation

  • 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.

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