title: Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia.
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.
authors.affiliation: Department of Genetics, INSERM U781, Université Paris Descartes, Hôpital Necker, Paris, France.
authors.forename: Slimane
authors.initials: S
authors.lastname: Allali
authors.forename: Carine
authors.initials: C
authors.lastname: Le Goff
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pressac-Diebold
authors.forename: Gwendoline
authors.initials: G
authors.lastname: Pfennig
authors.forename: Clémentine
authors.initials: C
authors.lastname: Mahaut
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dagoneau
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Alanay
authors.forename: Angela F
authors.initials: AF
authors.lastname: Brady
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Valérie
authors.initials: V
authors.lastname: Drouin-Garraud
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Flori
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
authors.forename: Raoul C
authors.initials: RC
authors.lastname: Hennekam
authors.forename: Jane
authors.initials: J
authors.lastname: Hurst
authors.forename: Deborah
authors.initials: D
authors.lastname: Krakow
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Klaske D
authors.initials: KD
authors.lastname: Lichtenbelt
authors.forename: Sally A
authors.initials: SA
authors.lastname: Lynch
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Kay
authors.initials: K
authors.lastname: MacDermot
authors.forename: Sahar
authors.initials: S
authors.lastname: Mansour
authors.forename: André
authors.initials: A
authors.lastname: Megarbané
authors.forename: Heloisa G
authors.initials: HG
authors.lastname: Santos
authors.forename: Miranda
authors.initials: M
authors.lastname: Splitt
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
authors.forename: Denise
authors.initials: D
authors.lastname: Williams
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D000293:Adolescent; D000328:Adult; D001848:Bone Diseases, Developmental; D002648:Child; D002675:Child, Preschool; D003238:Connective Tissue / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D004392:Dwarfism / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D005060:Europe / Q000453:epidemiology; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005124:Eye Abnormalities / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics; D007223:Infant; D007564:Japan / Q000453:epidemiology; D017880:Limb Deformities, Congenital; D008297:Male; D008877:Middle East / Q000453:epidemiology; D009154:Mutation; D010375:Pedigree; D012868:Skin Abnormalities / Q000235:genetics*
chemical_list: D016326:Extracellular Matrix Proteins