RESUMO
A decrease in the activity of ferrochelatase (FECH; EC 4.99.1.1), the terminal enzyme of the heme biosynthetic pathway, results in erythropoietic protoporphyria (EPP; MIM 177000). We analyzed the FECHgene in eight Japanese EPP patients from seven non-consanguineous families and found two distinct genomic DNA abnormalities. In six patients from five families, there was a G-to-A point-mutation at the first position of the intron 9 donor site; it resulted in aberrant splicing and skipping of exon 9 in FECH mRNA. In one patient, we found an A-to-G point-mutation 4 bases from the 3" terminus of intron 4 that led to the in-frame insertion of 3 bases in mRNA. No allelic anomalies, except for 3 single nucleotide polymorphisms were detected in another patient. We analyzed intron polymorphism at IVS3-48, known to be associated with the phenotypic expression of EPP, in these eight patients and 152 healthy Japanese volunteers. All patients were C/C homozygous for IVS3-48. The allelic frequency of IVS3-48C polymorphism in the healthy Japanese volunteers was 67.8% (103/152).
Assuntos
Povo Asiático/genética , Ferroquelatase/genética , Mutação/genética , Protoporfiria Eritropoética/enzimologia , Protoporfiria Eritropoética/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Íntrons/genética , Masculino , Polimorfismo Genético/genéticaRESUMO
PURPOSE: To report two independent Japanese patients with keratitis, ichthyosis, and deafness (KID) syndrome and severe corneal disorder. DESIGN: Observational case reports. METHODS: Clinical observation of a 5-year-old boy (Patient 1) and a 64-year-old man (Patient 2) with KID syndrome, presenting prominent corneal diseases. Molecular genetic assessment of the GJB2 gene encoding connexin-26 was performed. RESULTS: Patient 1 had bilateral diffuse superficial punctuate keratopathy with severe corneal neovascularization. He had a missense mutation of the GJB2 gene. Patient 2 had bilateral corneal stromal keratitis and right corneal ulceration with rupture of the Descemet membrane. He did not have any pathologic mutation of the GJB2 gene. The area of palisades of Vogt was diminished and tear production reduced in both patients. Topical eye drops, and corticosteroid or antibiotics, respectively, relieved them effectively. CONCLUSION: The impaired ocular surface regulating system might be a cause of corneal disease in KID syndrome and it can be treated by eye drops.
Assuntos
Úlcera da Córnea/complicações , Perda Auditiva Neurossensorial/complicações , Ictiose/complicações , Antibacterianos/uso terapêutico , Pré-Escolar , Conexina 26 , Conexinas/genética , Neovascularização da Córnea/complicações , Neovascularização da Córnea/tratamento farmacológico , Neovascularização da Córnea/genética , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/genética , Glucocorticoides/uso terapêutico , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/genética , Humanos , Ictiose/tratamento farmacológico , Ictiose/genética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Soluções Oftálmicas , SíndromeRESUMO
BACKGROUND: Most estrogen dermatitides are induced by local or systemic contact dermatitis where dendritic cells are central, and tamoxifen has a blocking effect on dendritic cells. METHODS: We present 5 cases of estrogen dermatitis in which the clinical features were prurigo, urticaria, acneiform eruption and annular erythema. RESULTS: Tamoxifen was effective in 3 of 4 cases. Three of 4 biopsy specimens showed the formation of Langerhans cell nests in the epidermis and hair follicles and perivascular infiltration of CD4+ and CD8+ lymphocytes in the dermis. CONCLUSION: These results suggest that a dendritic-cell-mediated allergic mechanism is involved in estrogen dermatitis.
Assuntos
Células Dendríticas/imunologia , Dermatite/tratamento farmacológico , Dermatite/etiologia , Estrogênios/efeitos adversos , Tamoxifeno/uso terapêutico , Adulto , Alérgenos , Células Apresentadoras de Antígenos/imunologia , Biópsia por Agulha , Dermatite/patologia , Estrogênios/metabolismo , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Testes do Emplastro , Recidiva , Medição de Risco , Estudos de Amostragem , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
X-linked hypohidrotic ectodermal dysplasia (XLHED; MIM 305100) is characterized by the absence or hypoplasia of hair, teeth, and sweat glands. The ED1 gene was identified as a responsive gene for XLHED. The patients were 2 Japanese brothers. Both had the same mutation in exon 1 of the ED1 gene, i.e. C deletion at nucleotide 49, which induced a frameshift starting from amino acid 17 and made a stop codon at amino acid 56, encoding the transmembrane site. The mutation caused the extracellular domain of ectodysplasin A to be completely absent. Their mother had a heterozygous allele; she congenitally lacked 1 tooth, and incisors appeared conical in form.
Assuntos
Displasia Ectodérmica/genética , Mutação da Fase de Leitura , Doenças Genéticas Ligadas ao Cromossomo X/genética , Proteínas de Membrana/genética , Pré-Escolar , Displasia Ectodérmica/patologia , Ectodisplasinas , Feminino , Heterozigoto , Humanos , Recém-Nascido , Masculino , Pele/patologiaRESUMO
X-linked hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is characterized by sparse hair, abnormal teeth and decreased sweating as a result of abnormal development of the sweat glands. Mutations in the ED1 gene, which encodes ectodysplasin-A (EDA), are responsible for XLHED. Ectodysplasin-A, a ligand for the EDA receptor, plays an important role in epidermal morphogenesis. We identified ED1 mutations including three novel mutations by sequencing genomic DNAs from eight unrelated Japanese XLHED families. Data from all reported mutations revealed that codon 156 in the furin subdomain is the most frequent site of change in EDA.
