Journal article
The phenotypic and genotypic spectra of ichthyosis with confetti plus novel genetic variation in the 3' end of KRT10: from disease to a syndrome.
- Spoerri I Research Group of Dermatology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
- Brena M Section of Dermatology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
- De Mesmaeker J Research Group of Dermatology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
- Schlipf N Institute of Human Genetics, University Medical Center Freiburg, Freiburg, Germany.
- Fischer J Institute of Human Genetics, University Medical Center Freiburg, Freiburg, Germany.
- Tadini G Section of Dermatology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
- Itin PH Dermatology, University Hospital Basel, Basel, Switzerland.
- Burger B Research Group of Dermatology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
- 2014-09-12
Published in:
- JAMA dermatology. - 2015
Adult
Child
Exons
Female
Genetic Variation
Genotype
Humans
Ichthyosiform Erythroderma, Congenital
Ichthyosis
Introns
Keratin-10
Male
Mutation
Phenotype
Polymorphism, Genetic
Syndrome
Young Adult
English
IMPORTANCE
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.
OBSERVATIONS
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 AND RELEVANCE
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.
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.
OBSERVATIONS
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 AND RELEVANCE
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1001/jamadermatol.2014.2526
- PMID 25210931
- Persistent URL
- https://sonar.ch/global/documents/238327
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