title: Mutation spectrum in the ABCC6 gene and genotype-phenotype correlations in a French cohort with pseudoxanthoma elasticum.
abstract: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder caused by variants in the ABCC6 gene. Ectopic mineralization of connective tissues leads to skin, eye, and cardiovascular manifestations with considerable phenotypic variability of unknown cause. We aimed to identify genotype-phenotype correlations in PXE.
  
  
  
  A molecular analysis was performed on 458 French PXE probands clinically evaluated using the Phenodex score (PS). Variant topographic analysis and genotype-phenotype correlation analysis were performed according to the number and type of identified variants.
  
  
  
  Complete molecular analysis of 306 cases allowed the identification of 538 mutational events (88% detection rate) with 142 distinct variants, of which 66 were novel. Missense variant distribution was specific to some regions and residues of ABCC6. For the 220 cases with a complete PS, there was a higher prevalence of eye features in Caucasian patients (P = 0.03) and more severe eye and vascular phenotype in patients with loss-of-function variants (P = 0.02 and 0.05, respectively). Nephrolithiases and strokes, absent from the PS, were prevalent features of the disorder (11 and 10%, respectively).
  
  
  
  We propose an updated PS including renal and neurological features and adaptation of follow-up according to the genetic and ethnic status of PXE-affected patients.Genet Med advance online publication 19 January 2017.
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Service de Médecine Vasculaire et Centre de Référence des Maladies Vasculaires Rares, Paris, France.|INSERM, U970, Paris Centre de Recherche Cardiovasculaire-PARCC, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
authors.forename: Anne
authors.identifier: 0000-0001-5703-3493
authors.initials: A
authors.lastname: Legrand
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, CEA Saclay, Gif-sur-Yvette, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Cornez
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Service de Médecine Vasculaire et Centre de Référence des Maladies Vasculaires Rares, Paris, France.
authors.forename: Wafa
authors.initials: W
authors.lastname: Samkari
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Service de Médecine Vasculaire et Centre de Référence des Maladies Vasculaires Rares, Paris, France.
authors.forename: Jean-Michael
authors.initials: JM
authors.lastname: Mazzella
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Service de Médecine Vasculaire et Centre de Référence des Maladies Vasculaires Rares, Paris, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Venisse
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Service de Médecine Vasculaire et Centre de Référence des Maladies Vasculaires Rares, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Boccio
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Service de Médecine Vasculaire et Centre de Référence des Maladies Vasculaires Rares, Paris, France.
authors.forename: Karine
authors.identifier: 0000-0002-5161-5473
authors.initials: K
authors.lastname: Auribault
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, UF de Génomique du Développement, Paris, France.
authors.forename: Boris
authors.identifier: 0000-0001-6172-8247
authors.initials: B
authors.lastname: Keren
authors.affiliation: AP-HP, Hôpital Raymond Poincaré, Département de Génétique, Garches, France.
authors.forename: Karelle
authors.initials: K
authors.lastname: Benistan
authors.affiliation: AP-HP, Hôpital Raymond Poincaré, Département de Génétique, Garches, France.|INSERM U1179, Paris-Saclay University, Montigny, France.|Université de Versailles Saint-Quentin-en-Yvelines, Montigny, France.
authors.forename: Dominique P
authors.identifier: 0000-0002-8355-007X
authors.initials: DP
authors.lastname: Germain
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Service de Médecine Vasculaire et Centre de Référence des Maladies Vasculaires Rares, Paris, France.|INSERM, U970, Paris Centre de Recherche Cardiovasculaire-PARCC, Paris, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Frank
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Service de Médecine Vasculaire et Centre de Référence des Maladies Vasculaires Rares, Paris, France.|INSERM, U970, Paris Centre de Recherche Cardiovasculaire-PARCC, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Service de Médecine Vasculaire et Centre de Référence des Maladies Vasculaires Rares, Paris, France.|INSERM, U970, Paris Centre de Recherche Cardiovasculaire-PARCC, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
authors.forename: Juliette
authors.identifier: 0000-0002-8947-6499
authors.initials: J
authors.lastname: Albuisson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005602:France / Q000453:epidemiology; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011561:Pseudoxanthoma Elasticum / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human