Assuntos
Alopecia/genética , Displasia Ectodérmica/genética , Hiperpigmentação/genética , Hipo-Hidrose/genética , Queratina-14/genética , Ceratodermia Palmar e Plantar/genética , Doenças da Unha/genética , Fenótipo , Neoplasias Cutâneas/genética , Alelos , Alopecia/diagnóstico , Alopecia/patologia , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/patologia , Mutação da Fase de Leitura , Humanos , Hiperpigmentação/diagnóstico , Hiperpigmentação/patologia , Hipo-Hidrose/diagnóstico , Hipo-Hidrose/patologia , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/patologia , Doenças da Unha/diagnóstico , Doenças da Unha/patologia , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaAssuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Pitiríase Rubra Pilar/genética , Psoríase/genética , Ubiquitina-Proteína Ligases/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Estudos de Casos e Controles , Feminino , Mutação da Fase de Leitura , Guanilato Ciclase/genética , Humanos , Masculino , Proteínas de Membrana/genética , FenótipoRESUMO
BACKGROUND: Epidermodysplasia verruciformis (EV) is a genodermatosis leading to infections with cutaneous HPV, persistent plane warts and a high rate of non-melanoma skin cancer (NMSC). Biallelic loss-of-function mutations in TMC6 and TMC8 are known to be causative. OBJECTIVE: The aim of this study was to report EV-causing mutations in four patients with EV and to give an overview of all described patients with EV. PATIENTS AND METHODS: We investigated four patients with classical features of EV from two families. All patients were affected by plane warts with typical EV histology since early childhood, and ß-HPVs were detected on their skin. One patient had recurring cutaneous squamous cell carcinomas (cSCC) and carcinomas in situ (Bowen type). We sequenced both TMC6/8 for disease-causing mutations and quantified levels of gene expression. We also performed a systematic literature review to discuss these patients in the context of previously reported cases, mutations already identified, as well as HPV types. RESULTS: Three patients of one family carried a homozygous splice site mutation in TMC8 resulting in aberrantly spliced transcripts that were not degraded. By contrast, no TMC6/8 mutation was detected in the patient from the other family. A systematic literature review revealed 501 described patients with EV. Around 40% of patients with EV analysed for genetic alterations carried no mutation in TMC6/8. While ß-HPVs were identified in the majority of cases, α-HPVs were detected in several individuals. CONCLUSION: The relatively high proportion of EV patients without mutation in TMC6/8 indicates the existence of EV-causing mutations in additional, presently unknown gene(s). However, a homozygous TMC8 splice site mutation in our patients resulted in aberrant transcripts which cannot retain the healthy phenotype. The literature review revealed that HPV-5 is the most commonly identified HPV in patients with EV, but HPV-3, HPV-14 and HPV-20 were unexpectedly identified more frequently than HPV-8.
Assuntos
Epidermodisplasia Verruciforme/genética , Proteínas de Membrana/genética , Mutação , Infecções por Papillomavirus/complicações , Splicing de RNA , Adolescente , Criança , Epidermodisplasia Verruciforme/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We established a flow cytometric lymphocyte proliferation test (LPT) for the detection of nickel (Ni) and palladium (Pd) sensitization. Eighty-one consecutive patients with an indication for patch test (PT) were tested by LPT with Ni (NiSO4 ) and Pd (Na2 PdCl4 and PdCl2 ) salts. The imprecision of the LPT was low (coefficient of variation 7.2%). Using PT as a diagnostic reference, the sensitivity and specificity of LPT were 74.4% and 80% for NiSO4 , 74.4% and 78.3% for Na2 PdCl4 , and 57.2% and 85.4% for PdCl2 , respectively. For both Ni and Pd, the likelihood ratio for a positive PT markedly increased with increasing LPT value. With medical history as a reference, the sensitivity and specificity were 40.6% and 82.1% for LPT and 59.4% and 89.7% for PT, respectively. Combination of LPT and PT resulted in a higher specificity of 95%, albeit lower sensitivity of 34.4%. In conclusion, flow cytometric LPT represents a reliable and useful method for the detection of Ni and Pd sensitization. LPT values correlate with PT results and, when used in combination with PT, increase test specificity.
Assuntos
Alérgenos/imunologia , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/imunologia , Ativação Linfocitária , Níquel/efeitos adversos , Paládio/efeitos adversos , Adulto , Idoso , Feminino , Citometria de Fluxo/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro/métodosRESUMO
Ichthyosis with confetti (IWC) was first described as ichthyose en confettis and subsequently as congenital reticular ichthyosiform erythroderma. Because of the development of hundreds to thousands of pale, normal-appearing confetti-like spots during childhood, the disease was named IWC. Patients with IWC show erythroderma, prominent scaling and palmoplantar keratoderma. Our female index patient was described in 1990 as the fourth patient reported worldwide; at that time she did not show any confetti-like spots. She was periodically examined at our clinic from birth until adulthood; hence we are able to describe the natural course of IWC in detail for the first time. We furthermore identified two novel deletions in KRT10, one of them leading to a frameshift and consequently to an arginine tail of keratin 10. Our report is the first independent confirmation of the KRT10 gene defect and revertant mosaicism mechanism in patients with IWC and it expands the clinical findings.
