Assuntos
DNA/metabolismo , Proteínas com Domínio T/química , Proteínas com Domínio T/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Cristalografia por Raios X , Síndrome de DiGeorge/genética , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Dobramento de Proteína , Multimerização Proteica , Estrutura Terciária de Proteína , Proteínas com Domínio T/genéticaRESUMO
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.