title: The phenotypic and genotypic spectra of ichthyosis with confetti plus novel genetic variation in the 3' end of KRT10: from disease to a syndrome.
abstract: OBJECTIVE
  Ichthyosis with confetti (IWC) is a genodermatosis caused by dominant negative mutations in the gene encoding keratin 10 (KRT10). We investigated clinical and genetic details of a substantial number of patients with IWC in order to define major and minor criteria for diagnosis of this rare disorder.
  
  
  METHODS
  Parallel clinical investigation of 6 patients with IWC revealed a novel spectrum of phenotypes. We found several features that qualify as major criteria for diagnosis, which are clearly and consistently associated with the condition. These included malformation of ears, hypoplasia of mammillae, and dorsal acral hypertrichosis. Genetic analysis of patients revealed several different frameshift mutations in intron 6 or exon 7 of KRT10. Analysis of this locus in 17 unrelated control individuals revealed 2 novel polymorphisms of KRT10.
  
  
  CONCLUSIONS
  We present for the first time to our knowledge the spectrum of clinical variability of IWC in 6 patients with confirmed mutations in KRT10. From this, we have extracted major and minor criteria to aid early and correct clinical diagnosis. Ectodermal malformations, present in all patients, suggest a novel classification of IWC as a syndrome. There is remarkable genetic variation at the IWC disease locus within control individuals from the general population.
authors.affiliation: Research Group of Dermatology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Iris
authors.initials: I
authors.lastname: Spoerri
authors.affiliation: Section of Dermatology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Brena
authors.affiliation: Research Group of Dermatology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Julie
authors.initials: J
authors.lastname: De Mesmaeker
authors.affiliation: Institute of Human Genetics, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Schlipf
authors.affiliation: Institute of Human Genetics, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Section of Dermatology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tadini
authors.affiliation: Dermatology, University Hospital Basel, Basel, Switzerland.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Itin
authors.affiliation: Research Group of Dermatology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Burger
mesh_terms: D000328:Adult; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D007057:Ichthyosis / Q000235:genetics*; D007438:Introns / Q000235:genetics; D053550:Keratin-10 / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D013577:Syndrome; D055815:Young Adult
chemical_list: C507493:KRT10 protein, human; D053550:Keratin-10