RESUMEN
Vascular type of Ehlers-Danlos syndrome (EDS) is the most severe type of EDS. It is an autosomal dominantly inherited disorder that results from mutations within the alpha1 type III collagen gene (COL3A1). We report a novel point mutation at donor splice-site in intron 42 of type III collagen gene resulting in the inclusion of 30 nucleotides into the mature mRNA in a case of vascular type of EDS. Since the age of approximately 8 months, the patient had had repeated episodes of purpura and gradually developed thin, translucent skin. She had a past history of pneumothorax. At the initial examination, she was found to have the characteristic facies, i.e., bird-like face, of the vascular type of EDS, thinning of skin over the limbs and trunk, and scattered purpura. The blood vessels under the skin could be clearly visualized. She showed hypermobility of the small joints of all the four limbs and acrogeric changes of the hands and feet. Analysis of the amount of collagen synthesized from cultured dermal fibroblasts by SDS-polyacrylamide gel electrophoresis and fluorography was conducted based on the clinical suspicion of the vascular type of EDS, and a marked reduction in the synthesis of type III collagen was observed. Genetic analysis of the COL3A1 revealed a novel point mutation at the donor splice-site of intron 42, which resulted in the inclusion of 30 nucleotides into the mature mRNA of one allele.
Asunto(s)
Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Fibroblastos/metabolismo , Células Cultivadas , Análisis Mutacional de ADN , Dermis/patología , Diagnóstico Diferencial , Síndrome de Ehlers-Danlos/patología , Síndrome de Ehlers-Danlos/fisiopatología , Femenino , Fibroblastos/patología , Dedos/anatomía & histología , Humanos , Inteínas/genética , Mutación Puntual/genética , Púrpura , Empalme del ARN , Adulto JovenRESUMEN
A 20-year-old man was referred to our hospital due to hemoptysis. Chest CT showed a ground-glass opacity, suggesting pulmonary bleeding; however, a diagnosis was not obtained. At a follow-up examination after 2 months, Chest CT showed improvement of the ground-glass opacity, however a cavitary nodule had newly appeared. Four months later, another new nodule was found on chest X-ray film. Video-assisted thoracoscopic lung biopsy was performed for pathological diagnosis; disruption of the pleural, lung and blood vessels, and pulmonary hematoma were found. We thought of the fragility of the pleuro-pulmonary connective tissue and also thought of the probability of Ehlers-Danlos syndrome (EDS). A biochemical analysis of cultured dermal fibroblasts and molecular biological examination revealed decreased production of type III collagen in fibroblasts and COL3A1 mutation. We diagnosed this case as vascular EDS. EDS is one of the differential diagnoses in patients presenting hemoptysis and pulmonary hematoma due to disruption of the lung.
Asunto(s)
Síndrome de Ehlers-Danlos/diagnóstico , Hematoma/etiología , Enfermedades Pulmonares/etiología , Hematoma/patología , Humanos , Enfermedades Pulmonares/patología , Masculino , Adulto JovenRESUMEN
A 17-year-old-man developed left-sided pneumothorax in 1995. Chest computed tomography (CT) showed a thick-walled cavity in the left lower lobe. Video-assisted thoracic surgery was performed, and pathologic findings of the resected lung showed a cavity, organizing hematoma, and a fibrous nodule. Fragility of connective tissue was suspected, and biochemical and molecular analysis showed reduction of type III collagen production and point mutation of the COL3A1 gene. The patient was diagnosed as having vascular-type Ehlers-Danlos syndrome (EDS). From 2002, the patient developed hemoptysis and bloody sputum once a year. Chest CT detected several nodules and cavities, which were regarded as hematomas with or without excretion. Several vascular changes including aneurysmal formations have been found since 2002, and an aneurysm of the left ulnar artery was resected. The patient continues to be followed regularly on an outpatient basis. We report a rare case of vascular-type EDS who developed pulmonary symptoms as an initial complication.
Asunto(s)
Síndrome de Ehlers-Danlos/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Neumotórax/diagnóstico por imagen , Adolescente , Síndrome de Ehlers-Danlos/complicaciones , Humanos , Enfermedades Pulmonares/complicaciones , Masculino , Neumotórax/complicaciones , Radiografía , RecurrenciaRESUMEN
Hailey-Hailey disease (HHD) is an autosomal dominant disorder with recurrent eruption of vesicles and bullae involving predominantly the neck, groin and axillary regions. Histopathology shows suprabasal cleavage in epidermal cells. Recent studies have revealed that HHD is caused by mutations in the ATP2C1 gene encoding a novel Ca(2+) pump. We analyzed mutations of the ATP2C1 gene in 2 Japanese patients with HHD. The diagnosis of HHD was made based on the characteristic clinical features and histopathological evidence. All 27 exons and flanking intron boundaries were amplified by polymerase chain reaction and products analyzed by sequencing. As a result, we identified a novel missense mutation (A1087G) in exon 13 of the ATP2C1 gene in a patient. This mutation led the amino acid change from Thrto Ala in the phosphorylation protein domain. Another patient showed no mutation of the gene. These results demonstrate that a spectrum of ATP2C1 gene mutations is present in Japanese HHD patients.
Asunto(s)
ATPasas Transportadoras de Calcio/genética , ADN/genética , Mutación Missense , Pénfigo Familiar Benigno/genética , Análisis Mutacional de ADN , Exones , Humanos , Japón , Pénfigo Familiar Benigno/patología , Reacción en Cadena de la PolimerasaRESUMEN
A 4-year-old Japanese boy, the youngest of three brothers, presented with ichthyosiform hyperkeratosis over his whole body, eczematous erythema with partial desquamation and erosion on the flexor side of the joints of extremities, the fossa axillaries, and the genital and buttock regions, and total hair loss on the scalp and the absence of eyebrows and eyelashes. In addition to the ichthyotic eruptions and hair abnormalities, he also had a ventricular septal defect, mental retardation, growth retardation, characteristic facial features such as a depressed nasal bridge, low-set ears, and ocular hypertelorism; therefore, he was diagnosed with cardio-facio-cutaneous (CFC) syndrome. The patient's family did not have a history of consanguineous marriage. The parents and the eldest son were healthy. However, the second son, also born with ichthyosiform hyperkeratosis over his whole body, total hair loss on the scalp, myocardial deficiency, mental retardation, growth retardation, and characteristic facial features, had died of pneumonia and sepsis at the age of 1.5 years. Because the middle brother had the same disease, the present case is considered to be a rare case of CFC syndrome with in a single generation.
Asunto(s)
Alopecia/patología , Queratosis/patología , Alopecia/genética , Preescolar , Facies , Defectos del Tabique Interventricular/genética , Defectos del Tabique Interventricular/patología , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Queratosis/genética , Masculino , Linaje , SíndromeRESUMEN
BACKGROUND: Fibrohistiocytic tumors are rare skin tumors. There are many kinds of fibrohistiocytic tumors. It is often difficult to differentiate dermatofibrosarcoma protuberans (DFSP) and malignant fibrous histiocytoma (MFH) from dermatofibroma (DF) and other benign tumors. OBJECTIVE: In this study, the possible usefulness of DNA ploidy for the differentiation was studied. METHODS: Five MFH, 9 DFSP, 3 DF, 2 lipofibromas and 2 scars were studied for DNA ploidy using a flow cytometer. RESULTS: All the 7 benign tumors showed a diploid pattern. Of 14 malignant fibrohistiocytic tumors, 8 cases (57.1%) showed an aneuploid and 6 a diploid pattern. Two of 5 MFH (40.0%) and 6 of 9 DFSP (66.7%) showed an aneuploid pattern. These results showed that fibrohistiocytic tumors with an aneuploid pattern are malignant, though those with a diploid pattern may be benign or malignant. CONCLUSION: Analysis of DNA ploidy using flow cytometry was concluded to be useful for the differentiation of malignant fibrohistiocytic tumors from benign ones.
Asunto(s)
ADN/genética , Dermatofibrosarcoma/genética , Histiocitoma Fibroso Benigno/genética , Neoplasias Cutáneas/genética , Dermatofibrosarcoma/diagnóstico , Citometría de Flujo , Histiocitoma Fibroso Benigno/diagnóstico , Humanos , Ploidias , Neoplasias Cutáneas/diagnósticoRESUMEN
1,25-Dihydroxyvitamin D is the biologically active form of vitamin D for the treatment of skin eruptions in patients with psoriasis. 1,25-(OH)(2)D(3) elicits its action on skin eruptions through the vitamin D receptor (VDR). Allelic frequencies of VDR were studied in 86 normal subjects and 50 patients with psoriasis. Genomic DNA was extracted from peripheral blood leukocytes and the VDR gene was amplified using a heminested polymerase chain reaction (PCR). The products were digested with respective restriction enzymes ApaI, TaqI and BsmI. The restriction fragment length polymorphisms (RFLP) were coded as Aa, Tt or Bb. The frequencies of ApaI, BsmI and TaqI RFLP genotypes in psoriasis patients showed no significant differences compared with normal controls. The frequency of the AA genotype was significantly higher in pustulosis palmaris et plantaris patients than in psoriasis vulgaris patients ( P<0.05), and in psoriasis vulgaris patients than in psoriasis pustulosa patients ( P<0.01). In patients with psoriasis, the levels of serum alanine 2-oxoglutarate aminotransferase (ALT) were significantly higher in patients with the AA genotype (54.0+/-22.0 IU/l, n=4) than in those with the aa genotype (24.0+/-15.9 IU/l, n=27; P<0.02). The distribution of ApaI, BsmI, TaqI RFLP VDR genotypes showed no significant relationship to the PASI score, serum aspartate 2-oxoglutarate aminotransferase or triglyceride levels, or age at onset. These results show that the VDR genotype contributes to the liver dysfunction in patients with psoriasis, although no correlation was found between VDR genotype and the skin eruptions of psoriasis.