title: Twenty patients including 7 probands with autosomal dominant cutis laxa confirm clinical and molecular homogeneity.
abstract: BACKGROUND
  Elastin gene mutations have been associated with a variety of phenotypes. Autosomal dominant cutis laxa (ADCL) is a rare disorder that presents with lax skin, typical facial characteristics, inguinal hernias, aortic root dilatation and pulmonary emphysema. In most patients, frameshift mutations are found in the 3' region of the elastin gene (exons 30-34) which result in a C-terminally extended protein, though exceptions have been reported.
  
  
  METHODS
  We clinically and molecularly characterized the thus far largest cohort of ADCL patients, consisting of 19 patients from six families and one sporadic patient.
  
  
  RESULTS
  Molecular analysis showed C-terminal frameshift mutations in exon 30, 32, and 34 of the elastin gene and identified a mutational hotspot in exon 32 (c.2262delA). This cohort confirms the previously reported clinical constellation of skin laxity (100%), inguinal hernias (51%), aortic root dilatation (55%) and emphysema (37%).
  
  
  CONCLUSIONS
  ADCL is a clinically and molecularly homogeneous disorder, but intra- and interfamilial variability in the severity of organ involvement needs to be taken into account. Regular cardiovascular and pulmonary evaluations are imperative in the clinical follow-up of these patients.
authors: Service de Dermatologie - Centre de référence national des Maladies Génétiques à Expression Cutanée MAGEC, INSERM U781, Hôpital Necker - Enfants Malades, Université Paris V-Descartes, 149, rue de Sèvres 75743 Paris Cedex 15, Paris, France. smail.hadj@inserm.fr
authors: Smail
authors: S
authors: Hadj-Rabia
authors: Bert L
authors: BL
authors: Callewaert
authors: Emmanuelle
authors: E
authors: Bourrat
authors: Marlies
authors: M
authors: Kempers
authors: Astrid S
authors: AS
authors: Plomp
authors: Valerie
authors: V
authors: Layet
authors: Deborah
authors: D
authors: Bartholdi
authors: Marjolijn
authors: M
authors: Renard
authors: Julie
authors: J
authors: De Backer
authors: Fransiska
authors: F
authors: Malfait
authors: Olivier M
authors: OM
authors: Vanakker
authors: Paul J
authors: PJ
authors: Coucke
authors: Anne M
authors: AM
authors: De Paepe
authors: Christine
authors: C
authors: Bodemer
mesh_terms: D003483:Cutis Laxa / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D006552:Hernia, Inguinal / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D011656:Pulmonary Emphysema / Q000235:genetics / Q000503:physiopathology; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology
chemical_list: D004549:Elastin