Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
Add more filters










Publication year range
1.
Int J Mol Sci ; 22(24)2021 Dec 13.
Article in English | MEDLINE | ID: mdl-34948168

ABSTRACT

Dystrophic epidermolysis bullosa (DEB) is an inheritable blistering disease caused by mutations in COL7A1, which encodes type VII collagen. To address the issue of genotype-phenotype correlations in DEB, analyzing the consequences of COL7A1 mutations using mRNA is indispensable. Herein we established a novel method for testing the effect of mutations in DEB using COL7A1 mRNA extracted from peripheral blood mononuclear cells (PBMCs). We investigated the consequences of four COL7A1 mutations (c.6573 + 1G > C, c.6216 + 5G > T, c.7270C > T and c.2527C > T) in three Japanese individuals with recessive DEB. The novel method detected the consequences of two recurrent COL7A1 mutations (c.6573 + 1G > C, c.6216 + 5G > T) and a novel COL7A1 mutation (c.7270C > T) accurately. In addition, it detected aberrant splicing resulting from a COL7A1 mutation (c.2527C > T) which was previously reported as a nonsense mutation. Furthermore, we revealed that type VII collagen-expressing cells in PBMCs have similar cell surface markers as mesenchymal stem cells; they were CD105+, CD29+, CD45-, and CD34-, suggesting that a small number of mesenchymal stem cells or mesenchymal stromal cells are circulating in the peripheral blood, which enables us to detect COL7A1 mRNA in PBMCs. Taken together, our novel method for analyzing mutation consequences using mRNA obtained from PBMCs in DEB will significantly contribute to genetic diagnoses and novel therapies for DEB.


Subject(s)
Collagen Type VII/genetics , DNA Mutational Analysis/methods , Epidermolysis Bullosa Dystrophica/genetics , Adult , Codon, Nonsense , Collagen Type VII/metabolism , Epidermolysis Bullosa Dystrophica/blood , Epidermolysis Bullosa Dystrophica/diagnosis , Female , Humans , Leukocytes, Mononuclear/metabolism , Male , Mutation/genetics , Pedigree , Phenotype , Polymorphism, Single Nucleotide/genetics , RNA Splicing , RNA, Messenger/analysis , RNA, Messenger/blood , RNA, Messenger/genetics
4.
Exp Dermatol ; 22(6): 433-5, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23711070

ABSTRACT

In the inherited blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB), there is clinical heterogeneity with variable scarring and susceptibility to malignancy. Currently, however, there are few biochemical markers of tissue inflammation or disease progression. We assessed whether the non-histone nuclear protein, high mobility group box 1 (HMGB1), which is released from necrotic cells (including keratinocytes in blister roofs), might be elevated in RDEB and whether this correlates with disease severity. We measured serum HMGB1 by ELISA in 26 RDEB individuals (median 21.0 ng/ml, range 3.6-54.9 ng/ml) and 23 healthy controls (median 3.6, range 3.4-5.9 ng/ml) and scored RDEB severity using the Birmingham Epidermolysis Bullosa Severity Score (BEBSS; mean 34/100, range 8-82). There was a positive relationship between the BEBSS and HMGB1 levels (r = 0.54, P = 0.004). This study indicates that serum HMGB1 levels may represent a new biomarker reflecting disease severity in RDEB.


Subject(s)
Biomarkers/blood , Epidermolysis Bullosa Dystrophica/blood , Epidermolysis Bullosa Dystrophica/genetics , Gene Expression Regulation , HMGB1 Protein/blood , HMGB1 Protein/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Disease Progression , Enzyme-Linked Immunosorbent Assay , Epidermolysis Bullosa Dystrophica/diagnosis , Female , Humans , Keratinocytes/metabolism , Male , Middle Aged , Necrosis , Severity of Illness Index , Young Adult
6.
J Eur Acad Dermatol Venereol ; 18(6): 649-53, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15482288

ABSTRACT

BACKGROUND: In recessive dystrophic epidermolysis bullosa (RDEB), a good nutritional balance is necessary to obtain healing of the chronic wounds. However, involvement of the oral mucosa and oesophagus stenosis may be responsible for severe nutritional deficiencies. OBJECTIVE: In order to propose an adapted nutritional management, we studied the vitamin and trace metal status of 14 RDEB patients. METHODS: Height and weight were measured. Plasma levels of albumin, iron, ferritin, calcium, parathyroid hormone (PTH), folates, vitamins C, D, B12, A, E, B1, B6, PP and B2, zinc, selenium, carnitine and copper were measured. RESULTS: Most patients had a significant growth retardation. We found iron, vitamin D, C, B6, PP, zinc and selenium deficiencies in 36-70% of the patients, without clinical expression, except in one case. Vitamin B1, 12, B2, A/RBP, E/lipids and carnitine were normal. The three patients with gastrostomy feeding had better growth but still a protein deficiency and sometimes vitamin C, B6, PP, zinc and carnitine deficiencies. CONCLUSION: Vitamin and trace metal deficiencies are frequent in RDEB, even in patients receiving gastrostomy feeding, and often go unrecognized. Regular nutritional evaluation is necessary. Dietary advice and supplements should be given. Enteral feeding by gastrostomy should be discussed in early childhood.


Subject(s)
Epidermolysis Bullosa Dystrophica/blood , Trace Elements/blood , Vitamins/blood , Adolescent , Adult , Avitaminosis/etiology , Child , Cross-Sectional Studies , Epidermolysis Bullosa Dystrophica/complications , Epidermolysis Bullosa Dystrophica/genetics , Female , Gastrostomy , Humans , Male , Nutritional Status
8.
Br J Dermatol ; 135(4): 603-6, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8915155

ABSTRACT

Two unrelated children with autosomal recessive dystrophic epidermolysis bullosa (RDEB) developed fatal dilated cardiomyopathy. Both were malnourished and had severe growth problems. We believe that the most likely cause for the cardiomyopathy is a micronutrient deficiency, most probably selenium deficiency, since the serum selenium level was found to be reduced in the case in whom we measured this, and in 14 of 25 other children with dystrophic epidermolysis bullosa. Echocardiographic screening of 18 other patients revealed no evidence of cardiomyopathy. We recommend careful attention to nutrition, with prospective monitoring of vitamins and micronutrients including selenium and carnitine, and regular echocardiographic screening of patients with severe RDEB.


Subject(s)
Cardiomyopathy, Dilated/etiology , Epidermolysis Bullosa Dystrophica/complications , Adolescent , Cardiomyopathy, Dilated/blood , Cardiomyopathy, Dilated/diagnostic imaging , Child , Child, Preschool , Epidermolysis Bullosa Dystrophica/blood , Fatal Outcome , Humans , Infant , Male , Selenium/blood , Selenium/deficiency , Ultrasonography
9.
Int J Dermatol ; 31(10): 730-2, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1399206

ABSTRACT

Three patients with severe recessive dystrophic epidermolysis bullosa were treated with oral phenytoin and palliative and supportive measures for variable periods. Their progress was compared with that of three milder cases managed only with palliative and supportive measures. The phenytoin-treated group showed marked decrease in blister count, increase in trauma tolerance, a rise in hemoglobin level, and considerable weight gain. The results support earlier reports that collagenase inhibitors are useful in controlling blister formation in recessive dystrophic epidermolysis bullosa.


Subject(s)
Epidermolysis Bullosa Dystrophica/drug therapy , Epidermolysis Bullosa Dystrophica/genetics , Phenytoin/therapeutic use , Administration, Oral , Epidermolysis Bullosa Dystrophica/blood , Female , Genes, Recessive , Hemoglobins/analysis , Humans , Infant , Infant, Newborn , Male , Phenytoin/administration & dosage , Phenytoin/blood , Weight Gain
10.
Pediatr Dermatol ; 9(3): 231-8, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1488371

ABSTRACT

In dystrophic epidermolysis bullosa (EB), a combination of diminished food intake and increased nutritional requirements commonly leads to malnourishment. Adequate nutrition in these patients could provide many benefits, including improved growth, accelerated healing, decreased susceptibility to infection, and enhanced well-being. We assessed nutrition status of children with dystrophic EB, and evaluated the benefits of nutritional advice in those who were considered malnourished. The majority of patients had inadequate intakes of a wide spectrum of nutrients, including those who appeared to be relatively mildly affected. We were unable to secure persisting substantial improvements in dietary intake despite thorough counseling. Adequate nutrition in patients with dystrophic EB depends on active nutritional support starting from birth. The need for more invasive techniques of nourishment, such as nasogastric and gastrostomy feeding, may have to be considered earlier than is currently the case.


Subject(s)
Child Nutrition Disorders/etiology , Epidermolysis Bullosa Dystrophica/complications , Body Height , Body Weight , Child , Child Nutrition Disorders/blood , Child Nutrition Disorders/drug therapy , Child, Preschool , Energy Intake , Epidermolysis Bullosa Dystrophica/blood , Epidermolysis Bullosa Dystrophica/drug therapy , Female , Humans , Infant , Iron/blood , Iron/therapeutic use , Male , Nutritional Requirements , Vitamins/therapeutic use , Zinc/blood , Zinc/therapeutic use
11.
Arch Dermatol ; 127(10): 1524-7, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1929459

ABSTRACT

BACKGROUND AND DESIGN: --Epidermolysis bullosa refers to a group of genetic diseases characterized by marked skin fragility and blister formation following minor mechanical trauma. The patients with recessive dystrophic epidermolysis bullosa (RDEB) are the most severely affected with marked internal and external blistering, scarring, and death at an early age, secondary to malnutrition, septicemia, and/or metastatic squamous cell carcinoma. An association between RDEB and HLA antigens was explored in 28 patients with RDEB and their family members. RESULTS: --Our data demonstrate that susceptibility to develop RDEB may be associated with the HLA complex. The gene frequencies of DR4 and DQw3 were much higher in the patients than expected. These increases were likely due to statistically significant excess of DR4 and DQw3 homozygotes in the patients. In addition, the observed frequencies of two HLA haplotypes: Bw62, DR4, DQw3 and Bw60, DR4, DQw3 were significantly higher than expected. CONCLUSION: --If these observations are confirmed in the larger series of patients, the association between RDEB and HLA complex may have clinical utility in genetic counseling of siblings of child-bearing age who are at risk of being carriers of RDEB.


Subject(s)
Epidermolysis Bullosa Dystrophica/genetics , HLA Antigens/blood , Adolescent , Adult , Child , Child, Preschool , Epidermolysis Bullosa Dystrophica/blood , Epidermolysis Bullosa Dystrophica/immunology , Genes, MHC Class I , Genes, MHC Class II , Haplotypes , Humans , Infant , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL
...