title: Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type.
abstract: The Ehlers-Danlos syndrome (EDS), dermatosparaxis type, is a recessively inherited connective tissue disorder caused by deficient activity of ADAMTS-2, an enzyme that cleaves the aminoterminal propeptide domain of types I, II, and III procollagen. Only 10 EDS dermatosparaxis patients have been reported, all presenting a recognizable phenotype with characteristic facial gestalt, extreme skin fragility and laxity, excessive bruising, and sometimes major complications due to visceral and vascular fragility.
  
  
  
  We report on five new EDS dermatosparaxis patients and provide a comprehensive overview of the current knowledge of the natural history of this condition.
  
  
  
  We identified three novel homozygous loss-of-function mutations (c.2927_2928delCT, p.(Pro976Argfs*42); c.669_670dupG, p.(Pro224Argfs*24); and c.2751-2A>T) and one compound heterozygous mutation (c.2T>C, p.? and c.884_887delTGAA, p.(Met295Thrfs26*)) in ADAMTS2 in five patients from four unrelated families. Three of these displayed a phenotype that was strikingly milder than that of previously reported patients.
  
  
  
  This study expands the clinical and molecular spectrum of the dermatosparaxis type of EDS to include a milder phenotypic variant and stresses the importance of good clinical criteria. To address this, we propose an updated set of criteria that accurately captures the multisystemic nature of the dermatosparaxis type of EDS.Genet Med 18 9, 882-891.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Tim
authors.identifier: 0000-0002-6424-4421
authors.initials: T
authors.lastname: Van Damme
authors.affiliation: Laboratory of Connective Tissues Biology, Tour de Pathologie, GIGA-Cancer, University of Liège, Liège, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Colige
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Delfien
authors.identifier: 0000-0001-9421-4496
authors.initials: D
authors.lastname: Syx
authors.affiliation: Division of Metabolism, Connective Tissue Unit, University Children's Hospital and Children's Research Centre, Zurich, Switzerland.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Giunta
authors.affiliation: Division of Metabolism, Connective Tissue Unit, University Children's Hospital and Children's Research Centre, Zurich, Switzerland.
authors.forename: Uschi
authors.identifier: 0000-0002-7350-5769
authors.initials: U
authors.lastname: Lindert
authors.affiliation: Division of Metabolism, Connective Tissue Unit, University Children's Hospital and Children's Research Centre, Zurich, Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Rohrbach
authors.affiliation: Department of Medical Genetics, Special Medical Center, Tehran, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Aryani
authors.affiliation: Pediatric Genetics Unit, Department of Pediatrics, Acibadem University School of Medicine, Istanbul, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Alanay
authors.affiliation: Department of Pediatric Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Pelin Özlem
authors.initials: PÖ
authors.lastname: Simsek-Kiper
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Hester Y
authors.initials: HY
authors.lastname: Kroes
authors.affiliation: Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.affiliation: 9Laboratory of Cell and Tissue Biology, GIGA-Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Marc
authors.identifier: 0000-0001-7736-8709
authors.initials: M
authors.lastname: Thiry
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sofie
authors.identifier: 0000-0003-4240-2772
authors.initials: S
authors.lastname: Symoens
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Anne
authors.identifier: 0000-0002-4134-5940
authors.initials: A
authors.lastname: De Paepe
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Fransiska
authors.initials: F
authors.lastname: Malfait
mesh_terms: D000071096:ADAMTS Proteins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004535:Ehlers-Danlos Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D000071096:ADAMTS Proteins; C000609307:ADAMTS2 protein, human