29 results on '"De Prost Y"'
Search Results
2. Genetic Study of Netherton Syndrome in a Large International Cohort
- Author
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Deraison, C, Descargues, P, Lacaze-Buzy, L, Besson, C, Mazarguil, A M, Mazereeuw-Hautier, J, Bourdon-Lanoy, E, de Prost, Y, Bodemer, C, and Hovnanian, A
- Published
- 2006
3. A Molecular Survey of 97 Families with Recessive and Dominant Dystrophic Epidermolysis Bullosa in French Reference Centres
- Author
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Titeux, M, Mejia, J E, Hadj-Rabia, S, Mazereeuw-Hautier, J, Lacaze-Buzy, L, Mazarguil, A M, Taïeb, A, de Prost, Y, Bodemer, C, and Hovnanian, A
- Published
- 2006
4. Kaposiform Haemangioendothelioma-spectrum Lesions with Kasabach-Merritt Phenomenon: Retrospective Analysis and Long-term Outcome
- Author
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J. Fontaine, Christine Bodemer, D. Orbach, Dominique Lasne, Sylvie Fraitag, Francis Brunelle, D. Hamel-Teillac, Olivia Boccara, Smail Hadj-Rabia, Bughin, and De Prost Y
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Time Factors ,Biopsy ,medicine.medical_treatment ,Kasabach-Merritt Phenomenon ,Antineoplastic Agents ,Kasabach-Merritt Syndrome ,Dermatology ,Fibrin Fibrinogen Degradation Products ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Adrenal Cortex Hormones ,medicine ,Coagulopathy ,Retrospective analysis ,Kaposiform haemangioendothelioma ,Humans ,Neoplasm Invasiveness ,Embolization ,Blood Coagulation ,Retrospective Studies ,medicine.diagnostic_test ,Platelet Count ,business.industry ,Infant, Newborn ,Infant ,Retrospective cohort study ,General Medicine ,Hospitals, Pediatric ,medicine.disease ,Combined Modality Therapy ,Embolization, Therapeutic ,Immunohistochemistry ,Surgery ,Treatment Outcome ,030220 oncology & carcinogenesis ,Hemangioendothelioma ,Female ,business ,Biomarkers ,Platelet Aggregation Inhibitors - Abstract
Kasabach-Merritt phenomenon (KMP) is a rare life-threatening vascular condition of infancy. Prognosis factors and long-term follow-up data are lacking. We retrospectively analysed the records of 24 infants (10 females, 14 males) treated for KMP in the Department of Dermatology of Necker-Enfants Malades Hospital, Paris, France, from 1984 to 2012. Mean duration of thrombocytopaenia (2,000-38,000 platelets/mm3, mean 10,500/µl) was 8.8 months (range 3 days-84 months), which correlated with tumour infiltration depth on imaging. D-dimer levels were always elevated, even before KMP onset. Each patient received a mean of 4.8 different treatments (range 1-10). Median follow-up was 6.5 years (range 2 months-22 years). All infants had residual cutaneous lesions, along with inflammatory manifestations (n = 9), elevated D-dimer (n = 5) and orthopaedic sequelae (n = 5). The permanent coagulopathy (elevated D-dimer) even after resolution of KMP suggests the presence of chronic low-grade platelet trapping, with possible sudden worsening, and raises the possibility of prophylactic anti-platelet therapy.
- Published
- 2016
5. Novel mutations in SPINK5 encoding a serine-protease inhibitor in Netherton syndrome, a severe congenital ichthyosis with hair abnormalities and atopic manifestations
- Author
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Bitoun, E., Chavanas, S., Irvine, A.D., Paradisi, M., Bodemer, C., Hamel-Teillac, D., Lonie, L., Ansai, S-i., Mitsuhashi, Y., Zimmer, M., de Prost, Y., Zambruno, G., Harper, J.I., and Hovnanian, A.
- Subjects
Genetic research -- Analysis ,Human genetics -- Research ,Genetic disorders -- Research ,Biological sciences - Published
- 2000
6. Homozygosity mapping of a locus for a novel form of syndromic ichthyosis to chromosome 3q27-q28
- Author
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Baala, L., Hadj-Rabia, S., Hamel-Teillac, D., Leal, S.M., Sefiani, A., de Prost, Y., Munnich, A., Lyonnet, S., and Vabres, P.
- Subjects
Genetic research -- Analysis ,Human genetics -- Research ,Biological sciences - Published
- 2000
7. Three novel point mutations in the keratinocyte transglutaminase (TGK) gene in lamellar ichthyosis: significance for mutant transcript level, TGK immunodetection and activity
- Author
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Petit E, Huber M, Rochat A, Bodemer C, Teillac-Hamel D, Jp, Müh, Revuz J, Barrandon Y, Lathrop M, de Prost Y, Hohl D, and Alain Hovnanian
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Adult ,Male ,Transglutaminases ,Staining and Labeling ,Genetic Linkage ,Immunoblotting ,Blotting, Northern ,Pedigree ,Genetics ,Humans ,Point Mutation ,Female ,RNA, Messenger ,Child ,Fluorescent Antibody Technique, Indirect ,Genetics (clinical) ,Ichthyosis, Lamellar - Abstract
We have investigated 8 patients from 7 unrelated families with lamellar ichthyosis (LI) for defects in the keratinocyte transglutaminase (TGK) gene. We have characterized three novel homozygous mutations and a previously reported splice acceptor site mutation. One patient showed a C-to-T change in the binding site for the transcription factor Sp1 within the promoter region. Another patient had a Gly 143-to-Glu mutation in exon 3 and a third patient, affected with a particular form of LI sparing the four limbs, demonstrated a Val382-to-Met mutation within exon 7. These three patients exhibited drastically reduced transglutaminase activity and an absence of detectable TGK polypeptide, as assessed by immunofluorescence and immunoblotting. Northern blot analysis showed that the Sp1 site mutation was associated with profound reduction of TGK transcript levels whereas normal transcript levels were observed for the two missense mutations. We hypothesize that the Sp1 site mutation impairs transcription of the TGK gene, whereas the two missense mutations induce structural changes leading to protein instability. Linkage to TGK was excluded in another family and no evidence for TGK defect was found in 3 other patients. These results further support the involvement of TGK in some patients with LI. They identify a TGK mutation as a cause for non-generalized LI and further delineate the molecular mechanisms underlying TGK deficiency in LI.
- Published
- 1997
8. Blepharophimosis, eczema, and growth and developmental delay in a young adult: late features of Dubowitz syndrome?
- Author
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Lyonnet, S, primary, Schwartz, G, additional, Gatin, G, additional, de Prost, Y, additional, Munnich, A, additional, and Le Merrer, M, additional
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- 1992
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9. Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: A tight junction disease
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Hadj-Rabia, S., Baala, L., Vabres, P., Hamel-Teillac, D., Jacquemin, E., Fabre, M., Lyonnet, S., de Prost, Y., Munnich, A., Hadchouel, M., and Smahi, A.
- Abstract
Background & Aims: Most human and animal cholestatic disorders are associated with changes in hepatocyte cytoskeleton and tight junctions (TJs). These changes are usually secondary and nonspecific phenomena, both in intra- and extrahepatic cholestasis. Recently, missense mutations in TJ protein 2 (ZO-2) have been identified in patients with familial hypercholanemia. In the liver, TJs separate bile flow from plasma and are composed of strands of claudins and occludin. We previously assigned a syndrome associating ichthyosis and neonatal sclerosing cholangitis (NISCH syndrome) to chromosome 3q27-q28. We considered claudin-1 to be a strong candidate gene based on its mapping to the minimum interval and on the expression pattern of the mouse ortholog. Methods: The 4 exons and intron-exon junctions of claudin-1 gene were amplified using standard polymerase chain reaction protocols and specific primers. Western blot analysis on cultured fibroblasts and immunohistochemistry on liver tissue section were performed using rabbit anti-claudin-1 antibodies. Results: We described in 4 patients, of 2 inbred kindred of Moroccan origin, a 2-bp deletion (200-201 TT) in exon 1 of the claudin-1 gene arising in a premature stop codon and resulting in total absence of claudin-1 protein in the liver and skin. Conclusions: Lack of claudin-1 in NISCH syndrome may lead to increased paracellular permeability between epithelial cells. Bile duct injury may be related to the absence of claudin-1 expression in cholangiocytes. Our observation, in conjunction with ZO-2-associated hypercholanemia, emphasizes the role played by TJ components in hereditary cholestasis.
- Published
- 2004
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10. Recurrent nonsense mutations within the type VII collagen gene in patients with severe recessive dystrophic epidermolysis bullosa
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Alain Hovnanian, Hilal L, Blanchet-Bardon C, de Prost Y, Am, Christiano, Uitto J, and Goossens M
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Male ,Adolescent ,Base Sequence ,DNA Mutational Analysis ,Molecular Sequence Data ,Arginine ,Polymerase Chain Reaction ,Epidermolysis Bullosa Dystrophica ,Pedigree ,Blotting, Southern ,Child, Preschool ,Humans ,Point Mutation ,Electrophoresis, Polyacrylamide Gel ,Female ,Collagen ,Child ,Algorithms ,DNA Primers ,Research Article - Abstract
The generalized mutilating form of recessive dystrophic epidermolysis bullosa (i.e., the Hallopeau-Siemens type; HS-RDEB) is a life-threatening disease characterized by extreme mucocutaneous fragility associated with absent or markedly altered anchoring fibrils (AF). Recently, we reported linkage between HS-RDEB and the type VII collagen gene (COL7A1), which encodes the major component of AF. In this study, we investigated 52 unrelated HS-RDEB patients and 2 patients with RDEB inversa for the presence, at CpG dinucleotides, of mutations changing CGA arginine codons to premature stop codons TGA within the COL7A1 gene. Eight exons containing 10 CGA codons located in the amino-terminal domain of the COL7A1 gene were studied. Mutation analysis was performed using denaturing gradient gel electrophoresis of PCR-amplified genomic fragments. Direct sequencing of PCR-amplified products with altered electrophoretic mobility led to the characterization of three premature stop codons, each in a single COL7A1 allele, in four patients. Two patients (one affected with HS-RDEB and the other with RDEB inversa) have the same C-to-T transition at arginine codon 109. Two other HS-RDEB patients have a C-to-T transition at arginine 1213 and 1216, respectively. These nonsense mutations predict the truncation of approximately 56%-92% of the polypeptide, including the collagenous and the noncollagenous NC-2 domains. On the basis of linkage analysis, which showed no evidence for locus heterogeneity in RDEB, it is expected that these patients are compound heterozygotes and have additional mutations on the other COL7A1 allele, leading to impaired AF formation.(ABSTRACT TRUNCATED AT 250 WORDS)
11. Adjuvant treatment with the bacterial lysate (OM-85) improves management of atopic dermatitis: A randomized study.
- Author
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Bodemer C, Guillet G, Cambazard F, Boralevi F, Ballarini S, Milliet C, Bertuccio P, La Vecchia C, Bach JF, and de Prost Y
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- Administration, Oral, Adrenal Cortex Hormones, Cell Extracts adverse effects, Child, Child, Preschool, Dermatitis, Atopic epidemiology, Dermatologic Agents therapeutic use, Double-Blind Method, Female, Humans, Infant, Male, Prevalence, Treatment Outcome, Adjuvants, Pharmaceutic therapeutic use, Cell Extracts therapeutic use, Dermatitis, Atopic drug therapy
- Abstract
Background: Environmental factors play a major role on atopic dermatitis (AD) which shows a constant rise in prevalence in western countries over the last decades. The Hygiene Hypothesis suggesting an inverse relationship between incidence of infections and the increase in atopic diseases in these countries, is one of the working hypothesis proposed to explain this trend., Objective: This study tested the efficacy and safety of oral administration of the bacterial lysate OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), in the treatment of established AD in children., Methods: Children aged 6 months to 7 years, with confirmed AD diagnosis, were randomized in a double-blind, placebo-controlled trial to receive, in addition to conventional treatment with emollients and topical corticosteroids, 3.5mg of the bacterial extract OM-85 or placebo daily for 9 months. The primary end-point was the difference between groups in the occurrence of new flares (NF) during the study period, evaluated by Hazard Ratio (HR) derived from conditional Cox proportional hazard regression models accounting for repeated events., Results: Among the 179 randomized children, 170 were analysed, 88 in the OM-85 and 82 in the placebo group. As expected most children in both treatment groups experienced at least 1 NF during the study period (75 (85%) patients in the OM-85 group and 72 (88%) in the placebo group). Patients treated with OM-85 as adjuvant therapy had significantly fewer and delayed NFs (HR of repeated flares = 0.80; 95% confidence interval (CI): 0.67-0.96), also when potential confounding factors, as family history of atopy and corticosteroids use, were taken into account (HR = 0.82; 95% CI: 0.69-0.98). No major side effect was reported, with comparable and good tolerability for OM-85 and placebo., Conclusions: Results show an adjuvant therapeutic effect of a well standardized bacterial lysate OM-85 on established AD.
- Published
- 2017
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12. Kaposiform Haemangioendothelioma-spectrum Lesions with Kasabach-Merritt Phenomenon: Retrospective Analysis and Long-term Outcome.
- Author
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Boccara O, Fraitag S, Lasne D, Fontaine J, Bughin V, Hamel-Teillac D, Orbach D, Brunelle F, de Prost Y, Hadj-Rabia S, and Bodemer C
- Subjects
- Adrenal Cortex Hormones therapeutic use, Biomarkers blood, Biopsy, Blood Coagulation, Combined Modality Therapy, Embolization, Therapeutic, Female, Fibrin Fibrinogen Degradation Products metabolism, Hemangioendothelioma blood, Hemangioendothelioma diagnosis, Hospitals, Pediatric, Humans, Immunohistochemistry, Infant, Infant, Newborn, Kasabach-Merritt Syndrome blood, Kasabach-Merritt Syndrome diagnosis, Male, Neoplasm Invasiveness, Platelet Count, Retrospective Studies, Time Factors, Treatment Outcome, Antineoplastic Agents therapeutic use, Hemangioendothelioma therapy, Kasabach-Merritt Syndrome therapy, Platelet Aggregation Inhibitors therapeutic use
- Abstract
Kasabach-Merritt phenomenon (KMP) is a rare life-threatening vascular condition of infancy. Prognosis factors and long-term follow-up data are lacking. We retrospectively analysed the records of 24 infants (10 females, 14 males) treated for KMP in the Department of Dermatology of Necker-Enfants Malades Hospital, Paris, France, from 1984 to 2012. Mean duration of thrombocytopaenia (2,000-38,000 platelets/mm3, mean 10,500/µl) was 8.8 months (range 3 days-84 months), which correlated with tumour infiltration depth on imaging. D-dimer levels were always elevated, even before KMP onset. Each patient received a mean of 4.8 different treatments (range 1-10). Median follow-up was 6.5 years (range 2 months-22 years). All infants had residual cutaneous lesions, along with inflammatory manifestations (n = 9), elevated D-dimer (n = 5) and orthopaedic sequelae (n = 5). The permanent coagulopathy (elevated D-dimer) even after resolution of KMP suggests the presence of chronic low-grade platelet trapping, with possible sudden worsening, and raises the possibility of prophylactic anti-platelet therapy.
- Published
- 2016
- Full Text
- View/download PDF
13. [Place of immunosuppressors in atopic dermatitis].
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de Prost Y
- Subjects
- Administration, Oral, Administration, Topical, Humans, Dermatitis, Atopic drug therapy, Immunosuppressive Agents therapeutic use
- Abstract
Use of immunosuppressors in the treatment of atopic dermatitis is an important innovation that reinforces the therapeutic arsenal in this chronic disease. Two such drugs are used topically for the treatment of atopic dermatitis. Tacrolimus exists in pommade form at a concentration of 0.1% for adults and 0.03% for children. Pimecrolimus, another calcineurine inhibitor with similar efficacy and tolerability, is not marketed in France. These products inhibit cytokine production by antigen-stimulated T lymphocytes. Their clinical efficacy has been demonstrated in many studies in the United States and Europe. They are particularly valuable for patients whose clinical course is marked by disease persistence and frequent flares, which would otherwise require almost continuous topical corticosteroid treatment. Topical calcineurine inhibitors may also have a significant benefit in patients with involvement of sensitive skin areas, such as around the eyes, face, neck and genital area, where systemic absorption and the risk of skin atrophy are particular concerns. The most frequent adverse effects are a local erythema-like reaction with burning and pruritus at the outset of treatment. No significant increase in bacterial or viral infections has been noted by comparison with control groups, and no systemic impact has been reported. However, these drugs should not be used in patients with a history of Kaposi-Juliusberg disease or in patients with herpes. Photoprotection measures must be respected. New trials with tacrolimus show that atopic lesions can be controlled by treating subclinical inflammation twice weekly between flares, thereby preventing flares and prolonging the flare-free interval. This new therapeutic approach is called proactive treatment. The efficacy of oral cyclosporine at 4-5 mg/kg/day in severe forms of atopic dermatitis is now well demonstrated. There is consistent evidence that oral cyclosporin is beneficial in patients whose disease is not adequately controlled by conventional topical therapies, leading to a significant improvement in health-related quality of life. Other immunosuppressors like methotrexate and some biologics (omalizumab, retuximab, etc.) show good efficacy during flares of severe forms, but larger comparative studies are needed before recommending these new treatments in severe atopic dermatitis.
- Published
- 2012
14. Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations.
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Bodemer C, Hermine O, Palmérini F, Yang Y, Grandpeix-Guyodo C, Leventhal PS, Hadj-Rabia S, Nasca L, Georgin-Lavialle S, Cohen-Akenine A, Launay JM, Barete S, Feger F, Arock M, Catteau B, Sans B, Stalder JF, Skowron F, Thomas L, Lorette G, Plantin P, Bordigoni P, Lortholary O, de Prost Y, Moussy A, Sobol H, and Dubreuil P
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- Adolescent, Age of Onset, Animals, Biopsy, COS Cells, Child, Child, Preschool, Chlorocebus aethiops, Clone Cells, Exons genetics, Female, Genomics, Genotype, Humans, Infant, Infant, Newborn, Male, Mast Cells physiology, Phenotype, Mast Cells pathology, Mastocytosis, Cutaneous genetics, Mastocytosis, Cutaneous pathology, Point Mutation, Proto-Oncogene Proteins c-kit genetics
- Abstract
Adult mastocytosis is an incurable clonal disease associated with c-KIT mutations, mostly in exon 17 (D816V). In contrast, pediatric mastocytosis often spontaneously regresses and is considered a reactive disease. Previous studies on childhood mastocytosis assessed only a few patients and focused primarily on codon 816 mutations, with various results. In this study, we analyzed the entire c-KIT sequence from cutaneous biopsies of 50 children with mastocytosis (ages 0-16 years). A mutation of codon 816 (exon 17) was found in 42% of cases, and mutations outside exon 17 were observed in 44%. Unexpectedly, half of the mutations were located in the fifth Ig loop of c-KIT's extracellular domain, which is encoded by exons 8 and 9. All mutations identified in this study were somatic and caused a constitutive activation of c-KIT. There was no clear phenotype-genotype correlation, no clear relationship between the mutations and familial versus spontaneous disease, and no significant change in the relative expression of the c-KIT GNNK+ and GNNK isoforms. These findings strongly support the idea that, although pediatric mastocytosis can spontaneously regress, it is a clonal disease most commonly associated with activating mutations in c-KIT.
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- 2010
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15. Epigallocatechin gallate's protective effect against MMP7 in recessive dystrophic epidermolysis bullosa patients.
- Author
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Changotade SI, Assoumou A, Guéniche F, Fioretti F, Séguier S, de Prost Y, Bodemer C, Godeau G, and Senni K
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- Adult, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, Blotting, Western, Catechin pharmacology, Collagen Type VII metabolism, Elastic Tissue pathology, Epidermolysis Bullosa Dystrophica genetics, Epidermolysis Bullosa Dystrophica pathology, Fibrillin-1, Fibrillins, Humans, Immunologic Techniques, Microfilament Proteins metabolism, Organ Culture Techniques, Skin enzymology, Skin pathology, Staining and Labeling, Time Factors, Tissue Distribution, Catechin analogs & derivatives, Epidermolysis Bullosa Dystrophica physiopathology, Genes, Recessive, Matrix Metalloproteinase 7 metabolism, Matrix Metalloproteinase Inhibitors, Protease Inhibitors pharmacology
- Abstract
The analysis of phenotype-genotype correlations of patients suffering from recessive dystrophic epidermolysis bullosa (RDEB) evidenced intrafamilial and interfamilial phenotype variability occurring for the same mutation of COL7A1; this underscores the role of other genetics environmental factors in the expressivity of the disease. In this work, we checked whether matrilysin 1 (matrix metalloproteinase (MMP)7) could take part in the epidermal detachment in RDEB. Furthermore, we investigated epigallocatechin 3 gallate (EGCG) to determine whether it could inhibit matrilysin activities on collagen type VII and fibrillin 1 known to be associated with the dermo-epidermal junction. In this work, matrilysin 1 was detected in affected and unaffected skins of the three RDEB patients; furthermore, MMP7 was shown to degrade ex vivo on healthy normal skin collagen VII and fibrillin 1. Thus, we suspect that MMP7 could take an active part in the epidermal detachment occurring during RDEB. We evidenced that EGCG in in vitro as well as in ex vivo experiments was a good inhibitor of MMP7 and developed a good protection of collagen type VII and fibrillin 1 susceptible of being degraded by MMP7. We therefore propose that EGCG could be used beneficially in patients suffering from RDEB.
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- 2007
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16. Three severe cases of EBS Dowling-Meara caused by missense and frameshift mutations in the keratin 14 gene.
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Titeux M, Mazereeuw-Hautier J, Hadj-Rabia S, Prost C, Tonasso L, Fraitag S, de Prost Y, Hovnanian A, and Bodemer C
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- Child, Preschool, Frameshift Mutation, Humans, Infant, Keratin-14, Keratins analysis, Keratins metabolism, Male, Mutation, Missense, Skin chemistry, Skin ultrastructure, Epidermolysis Bullosa Simplex genetics, Epidermolysis Bullosa Simplex pathology, Keratins genetics
- Abstract
We report three unrelated patients affected at birth with an unusually severe form of epidermolysis bullosa simplex Dowling-Meara type (EBS-DM) because of mutations in KRT14 encoding keratin 14. Two patients were heterozygous for the previously described p.M119T mutation. The third patient was heterozygous for a novel c.1246delC mutation predicting the replacement of the helix termination peptide and the tail domain by a 25 amino-acid aberrant carboxyterminal sequence. At age 2 years, patients carrying the p.M119T mutation still suffered from severe EBS-DM, whereas the patient harboring the c.1246delC mutation has improved over time. These cases illustrate genotype-phenotype correlations and have implications for genetic counselling of EBS.
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- 2006
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17. Presence of chimeric maternally derived keratinocytes in cutaneous inflammatory diseases of children: the example of pityriasis lichenoides.
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Khosrotehrani K, Guegan S, Fraitag S, Oster M, de Prost Y, Bodemer C, and Aractingi S
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- Antigens, CD1 analysis, Child, Child, Preschool, Chimerism, Dermatitis, Atopic genetics, Female, Humans, In Situ Hybridization, Fluorescence, Keratinocytes chemistry, Keratins analysis, Leukocyte Common Antigens analysis, Male, Pityriasis Lichenoides genetics, Pregnancy, Chimera, Dermatitis, Atopic pathology, Keratinocytes pathology, Maternal-Fetal Exchange, Pityriasis Lichenoides pathology
- Abstract
During pregnancy, maternal cells may enter the fetal circulation and persist until adulthood. The fate of these cells remains unknown. As unexplained T-cell-mediated conditions such as pityriasis lichenoides (PL) may occur in children, we aimed at identifying maternal cells in lesional skin of PL and controls. Archived skin biopsy specimens from young males with PL, atopic dermatitis, or normal skin were scanned for the presence of female (presumably maternal) cells using fluorescence in situ hybridization (FISH) with X and Y chromosome-specific probes. Phenotyping of maternal cells relied on FISH combined with anti-CD45, anti-CD1a, or anti-cytokeratin labelling, identifying leukocytes, Langerhans cells, and keratinocytes, respectively. Maternal cells were found in PL (11/12) and controls (4/7), but their average frequency was higher in PL: 99 per million cells as compared to 5 per million cells in controls (P = 0.005). In the epidermis, the maternal microchimeric cells were labelled by anti-cytokeratin in all cases. We identified maternally derived keratinocytes in the skin of male children with inflammatory skin disorders. These cells may either help repair the damaged skin or home initially in the skin and trigger a host (child) versus graft (mother) disease.
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- 2006
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18. Prognosis of subglottic haemangiomas associated with facial haemangiomas in a paediatric population: a preliminary study.
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Marianowski R, Le Ru Y, Hamel-Teillac D, De Prost Y, Manach Y, and Rassi S
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- Female, Hemangioma congenital, Humans, Infant, Infant, Newborn, Laryngeal Neoplasms congenital, Male, Prognosis, Retrospective Studies, Facial Neoplasms complications, Hemangioma complications, Laryngeal Neoplasms complications, Skin Neoplasms complications
- Published
- 2004
- Full Text
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19. Skin expression of metalloproteinases and tissue inhibitor of metalloproteinases in sibling patients with recessive dystrophic epidermolysis and intrafamilial phenotypic variation.
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Bodemer C, Tchen SI, Ghomrasseni S, Séguier S, Gaultier F, Fraitag S, de Prost Y, and Godeau G
- Subjects
- Adolescent, Adult, Child, Female, Humans, Male, Organ Culture Techniques, Phenotype, Time Factors, Tissue Inhibitor of Metalloproteinase-1 metabolism, Tissue Inhibitor of Metalloproteinase-2 metabolism, Epidermolysis Bullosa Dystrophica genetics, Epidermolysis Bullosa Dystrophica metabolism, Genes, Recessive, Metalloendopeptidases metabolism, Skin metabolism, Tissue Inhibitor of Metalloproteinases metabolism
- Abstract
A number of COL7A1 mutations have now been reported in recessive dystrophic epidermolysis bullosa patients, and the analysis of phenotype-genotype correlations showed evidence for interfamilial and intrafamilial phenotypic variability, occurring for the same mutation. Collagenase and stromelysin activities have been found to be overexpressed in skin cultures of some recessive dystrophic epidermolysis bullosa patients, and tissue destruction in the disease process might result from an imbalance of metalloproteinases (MMP) over tissueinhibitor of metalloproteinases (TIMP). So we suspected that the phenotypic variability for the same mutation could be linked to other genetic or environmental factors, as a particular balance between MMP and TIMP. Organ cultures were performed using explants from the skin of three patients from the same family with recessive dystrophic epidermolysis bullosa to reveal and quantify the expression of MMP-1 (collagenase 1), MMP-2 and MMP-9 (gelatinases A and B), MMP-3 (stromelysin 1), TIMP-1, and TIMP-2, and to compare the results with those obtained with two human control skins, with the same experimental conditions. Increased amounts of all metalloproteinases investigated were observed in the skin of the three recessive dystrophic epidermolysis bullosa affected sibling brothers, both in lesioned and in apparently nonlesioned skin, compared with controls. The amounts of MMP-1, MMP-2, MMP-3, and MMP-9 increased particularly in the skin of the more clinically affected patient. Furthermore for this patient we evidenced higher amounts of MMP-1 and also a lower TIMP-1 amount in his unlesioned and lesioned skin compared with the other two affected patients and with healthy control donors. So we can suspect that recessive dystrophic epidermolysis bullosa phenotypic variability could be related to patients' collagenase activity heterogeneity, linked to imbalance between MMP-1 and TIMP-1.
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- 2003
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20. Homozygosity mapping of a locus for a novel syndromic ichthyosis to chromosome 3q27-q28.
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Baala L, Hadj-Rabia S, Hamel-Teillac D, Hadchouel M, Prost C, Leal SM, Jacquemin E, Sefiani A, De Prost Y, Courtois G, Munnich A, Lyonnet S, and Vabres P
- Subjects
- Adolescent, Child, Child, Preschool, Cholangitis, Sclerosing genetics, Cholangitis, Sclerosing pathology, Chromosome Mapping, Consanguinity, Family Health, Female, Founder Effect, Homozygote, Humans, Hypotrichosis genetics, Hypotrichosis pathology, Ichthyosis pathology, Keratinocytes pathology, Leukocytes pathology, Male, Morocco, Pedigree, Scalp, Chromosomes, Human, Pair 3, Ichthyosis genetics
- Abstract
Ichthyosis is a heterogeneous group of skin disorders characterized by abnormal epidermal scaling. Occasionally, extracutaneous features are associated. A novel autosomal recessive ichthyosis syndrome is described here with scalp hypotrichosis, scarring alopecia, sclerosing cholangitis, and leukocyte vacuolization in two inbred kindreds of Moroccan origin. We also report the mapping of the diseased gene to a 21.2 cM interval of chromosome 3q27-q28. Homo zygosity for polymorphic markers has enabled us to reduce the genetic interval to a 16.2 cM region. Furthermore, comparison of mutant chromosomes in the two families has suggested a common ancestral mutant haplotype. This linkage disequilibrium has reduced the genetic interval encompassing the diseased gene to less than 9.5 cM maximum. Further study of additional families from the same geographic area will hopefully reduce the genetic interval as well as help in the cloning of the gene involved in this rare disorder.
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- 2002
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21. Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families.
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Bitoun E, Chavanas S, Irvine AD, Lonie L, Bodemer C, Paradisi M, Hamel-Teillac D, Ansai S, Mitsuhashi Y, Taïeb A, de Prost Y, Zambruno G, Harper JI, and Hovnanian A
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Codon, Nonsense genetics, Congenital Abnormalities genetics, DNA Transposable Elements, Exons genetics, Gene Deletion, Genome, Genotype, Humans, Infant, Molecular Sequence Data, Polymorphism, Genetic genetics, Proteinase Inhibitory Proteins, Secretory, RNA Splice Sites genetics, RNA, Messenger metabolism, Serine Peptidase Inhibitor Kazal-Type 5, Syndrome, Carrier Proteins, Hair abnormalities, Hypersensitivity genetics, Ichthyosiform Erythroderma, Congenital genetics, Mutation genetics, Serine Proteinase Inhibitors genetics
- Abstract
Netherton syndrome is a severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome. Here we describe the intron-exon organization of the gene and characterize the SPINK5 mutations in patients from 21 families of different geographic origin, using denaturing high performance liquid chromatography and direct sequencing. We identified 18 mutations, of which 13 were novel and seven (39%) were recurrent. The majority of the mutations were clustered between exons 1-8 and exons 21-26. They comprised four nonsense mutations (22%), eight frameshift insertions or deletions (44%), and six splice-site defects (33%). All mutations predict the formation of premature termination codons. Northern blot analysis showed variable reduction of SPINK5 mutant transcript levels, suggesting variable efficiency of nonsense-mediated mRNA decay. Seven patients were homozygotes, eight were compound heterozygotes, and five were heterozygotes with only one identifiable SPINK5 mutation. Five mutations, one of which resulted in perinatal lethal disease in three families, were associated with certain ethnic groups. We also describe 45 intragenic polymorphisms in the patients studied. The clinical features of erythroderma, trichorrhexis invaginata, and atopic manifestations were present in the majority of affected individuals and ichthyosis linearis circumflexa was seen in 12 out of 24 patients. Interfamilial and intrafamilial variation in disease severity was observed, with no clear correlation between mutations and phenotype, suggesting that the degree of severity may be affected by other factors.
- Published
- 2002
- Full Text
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22. Genetic bases of severe junctional epidermolysis bullosa presenting spontaneous amelioration with aging.
- Author
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Gache Y, Allegra M, Bodemer C, Pisani-Spadafora A, de Prost Y, Ortonne JP, and Meneguzzi G
- Subjects
- Age Factors, Base Sequence, Cell Adhesion Molecules genetics, Cells, Cultured, Child, Codon, Nonsense, DNA chemistry, DNA genetics, DNA Mutational Analysis, Epidermolysis Bullosa, Junctional pathology, Family Health, Female, Gene Expression, Humans, Keratinocytes cytology, Keratinocytes metabolism, Laminin genetics, Male, Mutation, Pedigree, RNA, Messenger genetics, RNA, Messenger metabolism, Sequence Deletion, Severity of Illness Index, Skin metabolism, Kalinin, Epidermolysis Bullosa, Junctional genetics, Skin pathology
- Abstract
Change of the clinical picture with aging is noted in some patients suffering from junctional epidermolysis bullosa (JEB), an inherited blistering disorder caused by extensive disadhesion of the epithelia. We have studied a patient born with severe JEB associated with absent expression of laminin 5. A remarkable reduction of the blistering tendency was observed with aging that correlated with a restored expression of immunoreactive laminin 5 molecules. Genetic analysis of the gene LAMB3 detected compound heterozygosity for the nonsense mutation R635X and a novel 2 bp deletion (1587delAG) resulting in a downstream premature termination codon. RT-PCR amplification of total RNA purified from skin biopsies demonstrated that the mutated beta3 mRNAs underwent rapid decay shortly after birth, and that illegitimate splicing of the mRNA carrying mutation 1587delAG generated a new internally shortened beta3 transcript with advancing age. Our genetic and biochemical data show that (i) the illegitimate splicing of the beta3 pre-mRNA results in synthesis and secretion of a laminin 5 heterotrimer with an internally deleted beta3 polypeptide, (ii) expression of the mutated beta3 polypeptide is up-regulated in the basal keratinocytes with high proliferative potential, (iii) absence of the N-terminal region of the beta3 rod domain II thought to stabilize the tertiary structure of the laminin 5 is not required for the assembly of the protein and (iv) the mutant laminin 5 retains its adhesive potential. Our results demonstrate that mRNA rescue may underlie the evolution of the clinical phenotype in inherited skin conditions.
- Published
- 2001
- Full Text
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23. Linkage of Marie-Unna hypotrichosis locus to chromosome 8p21 and exclusion of 10 genes including the hairless gene by mutation analysis.
- Author
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Lefevre P, Rochat A, Bodemer C, Vabres P, Barrandon Y, de Prost Y, Garner C, and Hovnanian A
- Subjects
- Chromosome Mapping, DNA chemistry, DNA genetics, DNA Mutational Analysis, Family Health, Female, Genetic Linkage, Humans, Lod Score, Male, Microsatellite Repeats, Middle Aged, Mutation, Pedigree, Alopecia genetics, Chromosomes, Human, Pair 8 genetics, Hypotrichosis genetics
- Abstract
Marie-Unna hypotrichosis (MU) is a rare autosomal dominant congenital alopecia characterised by progressive hair loss starting in early childhood, often aggravated at puberty and leading to scarring alopecia of variable severity. We have studied three multigeneration families of Belgian, British and French descent. The human genome was screened with microsatellite markers spaced at 10-cM intervals and significant evidence for linkage to the disease was observed on chromosome 8p21, with a maximum two-point lod score of 8.26 for D8S1786 at a recombination fraction of 0. Recombinants narrowed the region of interest to a genetic interval of about 12 cM flanked by markers D8S280 and D8S1839. This interval contains the hairless gene which is mutated in autosomal recessive congenital atrichia. Sequencing of the entire coding region and intronic splice sites of the hairless gene in these three families and in two unrelated familial cases revealed several polymorphic changes but failed to identify causative mutations. Nine other genes located within this region and expressed in skin were also excluded by mutation analysis. Together with a recent linkage study performed in a Dutch and a British family by van Steensel et al these results provide evidence for the presence of a gene distinct from hairless in chromosomal region 8p21 playing an important role in hair follicle biology.
- Published
- 2000
- Full Text
- View/download PDF
24. Role of cytotoxic T cells in chronic alopecia areata.
- Author
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Bodemer C, Peuchmaur M, Fraitaig S, Chatenoud L, Brousse N, and De Prost Y
- Subjects
- Alopecia Areata pathology, Antigens, CD metabolism, Chronic Disease, Cytokines genetics, HLA-DR Antigens metabolism, Humans, Immunohistochemistry, In Situ Hybridization, RNA, Messenger metabolism, Scalp metabolism, Scalp pathology, T-Lymphocytes, Cytotoxic metabolism, T-Lymphocytes, Cytotoxic pathology, Alopecia Areata physiopathology, T-Lymphocytes, Cytotoxic physiology
- Abstract
Cytokines play a role in alopecia areata. We used immunohistochemical and in situ hybridization studies to demonstrate the persistence of pro-inflammatory as well as apoptotic mechanisms in skin biopsies from patients with chronic alopecia areata. In situ hybridization allows the visualization of the distribution of immunocompetent cells in vivo. We studied skin biopsies from 11 untreated alopecia areata patients and two normal controls. In situ hybridization was performed on frozen sections using 35S-radio-labeled riboprobes, specific for IL-1beta, IL-2, IL-6, INFgamma, and granzyme B mRNA. Immunohistochemistry was carried out using an anti-IL-1beta monoclonal antibody, and a monoclonal antibody directed against the human Fas protein. We demonstrated the presence of cells labeled with IL-1beta, IL-6, INFgamma, and granzyme B antisense probes. Similarly, cells labeled with anti-IL-1beta were found in 10 of 11 cases. The labeled cells were located in the mononuclear peri- and intrafollicular infiltrate. Cells expressing granzyme B were found in close contact with the follicle. Fas positivity was demonstrated in four of four cases at the level of the cytoplasmic membrane of the hair follicle keratinocytes. These results, based on visualizing the labeled cells, demonstrate that pro-inflammatory cytokines are produced by the mononuclear cell infiltrate in close contact with follicles in alopecia areata. Furthermore, they demonstrate for the first time that apoptotic mechanisms involving granzyme B and Fas-Fas ligand pathways may play a major role in the persistence of chronic alopecia areata.
- Published
- 2000
- Full Text
- View/download PDF
25. Deletions within COL7A1 exons distant from consensus splice sites alter splicing and produce shortened polypeptides in dominant dystrophic epidermolysis bullosa.
- Author
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Sakuntabhai A, Hammami-Hauasli N, Bodemer C, Rochat A, Prost C, Barrandon Y, de Prost Y, Lathrop M, Wojnarowska F, Bruckner-Tuderman L, and Hovnanian A
- Subjects
- Adult, Amino Acid Sequence, Biopsy, Cells, Cultured, Child, Consensus Sequence, Epidermolysis Bullosa Dystrophica metabolism, Epidermolysis Bullosa Dystrophica pathology, Female, Genes, Dominant, Genotype, Heterozygote, Humans, Introns, Keratinocytes metabolism, Male, Pedigree, Phenotype, Polymerase Chain Reaction, Repetitive Sequences, Nucleic Acid, Skin pathology, Skin ultrastructure, Alternative Splicing, Collagen genetics, Epidermolysis Bullosa Dystrophica genetics, Exons, Procollagen genetics, Sequence Deletion
- Abstract
We describe two familial cases of dominant dystrophic epidermolysis bullosa (DDEB) that are heterozygous for deletions in COL7A1 that alter splicing, despite intact consensus splice-site sequences. One patient shows a 28-bp genomic deletion (6081del28) in exon 73 associated with the activation of a cryptic donor splice site within this exon; the combination of both defects restores the phase and replaces the last 11 Gly-X-Y repeats of exon 73 by a noncollagenous sequence, Glu-Ser-Leu. The second patient demonstrates a 27-bp deletion in exon 87 (6847del27), causing in-frame skipping of this exon; consensus splice sites, putative branch sites, and introns flanking exons 73 and 87 showed a normal sequence. Keratinocytes from the probands synthesized normal and shortened type VII collagen polypeptides and showed intracellular accumulation of type VII procollagen molecules. This first report of genomic deletions in COL7A1 in DDEB suggests a role for exonic sequences in the control of splicing of COL7A1 pre-mRNA and provides evidence that shortened type VII collagen polypeptides can alter, in a dominant manner, anchoring-fibril formation and can cause DDEB of differing severity.
- Published
- 1998
- Full Text
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26. Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation.
- Author
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Hovnanian A, Rochat A, Bodemer C, Petit E, Rivers CA, Prost C, Fraitag S, Christiano AM, Uitto J, Lathrop M, Barrandon Y, and de Prost Y
- Subjects
- Alleles, Arginine genetics, Basement Membrane, Codon, Terminator genetics, Collagen analysis, Epidermolysis Bullosa Dystrophica pathology, Gene Expression, Genes, Recessive genetics, Genotype, Glycine genetics, Humans, Keratinocytes, RNA Splicing genetics, RNA, Messenger genetics, Skin chemistry, Skin ultrastructure, Collagen genetics, Epidermolysis Bullosa Dystrophica genetics, Mutation genetics, Skin pathology
- Abstract
We have characterized 21 mutations in the type VII collagen gene (COL7A1) encoding the anchoring fibrils, 18 of which were not previously reported, in patients from 15 unrelated families with recessive dystrophic epidermolysis bullosa (RDEB). COL7A1 mutations in both alleles were identified by screening the 118 exons of COL7A1 and flanking intron regions. Fourteen mutations created premature termination codons (PTCs) and consisted of nonsense mutations, small insertions, deletions, and splice-site mutations. A further seven mutations predicted glycine or arginine substitutions in the collagenous domain of the molecule. Two mutations were found in more than one family reported in this study, and six of the seven missense mutations showed clustering within exons 72-74 next to the hinge region of the protein. Patients who were homozygous or compound heterozygotes for mutations leading to PTCs displayed both absence or drastic reduction of COL7A1 transcripts and undetectable type VII collagen protein in skin. In contrast, missense mutations were associated with clearly detectable COL7A1 transcripts and with normal or reduced expression of type VII collagen protein at the dermo/epidermal junction. Our results provide evidence for at least two distinct molecular mechanisms underlying defective anchoring fibril formation in RDEB: one involving PTCs leading to mRNA instability and absence of protein synthesis, the other implicating missense mutations resulting in the synthesis of type VII collagen polypeptide with decreased stability and/or altered function. Genotype-phenotype correlations suggested that the nature and location of these mutations are important determinants of the disease phenotype and showed evidence for interfamilial phenotypic variability.
- Published
- 1997
- Full Text
- View/download PDF
27. DNA-based prenatal diagnosis of generalized recessive dystrophic epidermolysis bullosa in six pregnancies at risk for recurrence.
- Author
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Hovnanian A, Hilal L, Blanchet-Bardon C, Bodemer C, de Prost Y, Stark CA, Christiano AM, Dommergues M, Terwilliger JD, and Izquierdo L
- Subjects
- Base Sequence, Collagen genetics, Epidermolysis Bullosa Dystrophica genetics, Female, Genetic Linkage, Genetic Markers, Genotype, Humans, Molecular Sequence Data, Mutation, Pregnancy, Recurrence, Epidermolysis Bullosa Dystrophica diagnosis, Prenatal Diagnosis
- Abstract
Linkage analyses in generalized recessive dystrophic epidermolysis bullosa (RDEB) have implicated the type VII collagen gene (COL7A1), which encodes the major component of anchoring fibrils, and recent identification of COL7A1 mutations has provided direct evidence for COL7A1 defects underlying RDEB. In this study, COL7A1 gene analysis was used to successfully perform first-trimester prenatal diagnosis in six families at risk for recurrence of the disease. In four families, three affected with the most severe variant of RDEB (the Hallopeau-Siemens form, HS-RDEB) and one with generalized nonmutilating RDEB, prenatal diagnosis was established by linkage analysis using polymerase chain reaction-based detection of PvuII and AluI intragenic restriction fragment length polymorphism. In two other HS-RDEB families, prenatal diagnosis was carried out by direct detection of mutations in COL7A1, using denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genomic fragments. Analysis of fetal DNA from chorionic villus biopsy or from amniotic fluid cells showed that the fetus had inherited at least one normal COL7A1 allele in all cases. Therefore, the fetus was predicted to be unaffected in the six pregnancies, and this has been confirmed in the newborn infants. Genotype analysis with COL7A1 polymorphic markers, or direct COL7A1 mutation detection in families at risk for the disease, represent early and rapid diagnostic alternatives to second-trimester evaluation of fetal skin samples, and thus offer a major advance in prenatal diagnosis of this life-threatening form of epidermolysis bullosa.
- Published
- 1995
- Full Text
- View/download PDF
28. Recurrent nonsense mutations within the type VII collagen gene in patients with severe recessive dystrophic epidermolysis bullosa.
- Author
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Hovnanian A, Hilal L, Blanchet-Bardon C, de Prost Y, Christiano AM, Uitto J, and Goossens M
- Subjects
- Adolescent, Algorithms, Arginine genetics, Base Sequence, Blotting, Southern, Child, Child, Preschool, DNA Mutational Analysis methods, DNA Primers, Electrophoresis, Polyacrylamide Gel methods, Female, Humans, Male, Molecular Sequence Data, Pedigree, Polymerase Chain Reaction, Collagen genetics, Epidermolysis Bullosa Dystrophica genetics, Point Mutation
- Abstract
The generalized mutilating form of recessive dystrophic epidermolysis bullosa (i.e., the Hallopeau-Siemens type; HS-RDEB) is a life-threatening disease characterized by extreme mucocutaneous fragility associated with absent or markedly altered anchoring fibrils (AF). Recently, we reported linkage between HS-RDEB and the type VII collagen gene (COL7A1), which encodes the major component of AF. In this study, we investigated 52 unrelated HS-RDEB patients and 2 patients with RDEB inversa for the presence, at CpG dinucleotides, of mutations changing CGA arginine codons to premature stop codons TGA within the COL7A1 gene. Eight exons containing 10 CGA codons located in the amino-terminal domain of the COL7A1 gene were studied. Mutation analysis was performed using denaturing gradient gel electrophoresis of PCR-amplified genomic fragments. Direct sequencing of PCR-amplified products with altered electrophoretic mobility led to the characterization of three premature stop codons, each in a single COL7A1 allele, in four patients. Two patients (one affected with HS-RDEB and the other with RDEB inversa) have the same C-to-T transition at arginine codon 109. Two other HS-RDEB patients have a C-to-T transition at arginine 1213 and 1216, respectively. These nonsense mutations predict the truncation of approximately 56%-92% of the polypeptide, including the collagenous and the noncollagenous NC-2 domains. On the basis of linkage analysis, which showed no evidence for locus heterogeneity in RDEB, it is expected that these patients are compound heterozygotes and have additional mutations on the other COL7A1 allele, leading to impaired AF formation.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
29. Reversal effects of topical retinoic acid on the skin of kidney transplant recipients under systemic corticotherapy.
- Author
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De Lacharriére O, Escoffier C, Gracia AM, Teillac D, Saint Léger D, Berrebi C, Debure A, Lévêque JL, Kreis H, and De Prost Y
- Subjects
- Administration, Topical, Adrenal Cortex Hormones pharmacology, Adult, Female, Graft Rejection drug effects, Humans, Male, Microscopy, Electron, Middle Aged, Skin pathology, Skin ultrastructure, Tretinoin administration & dosage, Adrenal Cortex Hormones therapeutic use, Kidney Transplantation pathology, Skin drug effects, Tretinoin pharmacology
- Abstract
The systemic long-term corticosteroid treatment administered to kidney graft recipients (KGR) within the framework of the required immunosuppressive therapy induces an atrophy of the skin, from the sixth month onwards. We studied the effect of topical all-trans retinoic acid (0.05%; Galderma Labs.) applied to the forearms of 27 KGR (14 men, 13 women) over a 6-month period. Twenty-four subjects completed the trial. The following results were obtained in the treated forearm versus the untreated forearm (excipient alone): clinically, an increase in skin thickness; by noninvasive techniques, an increase in skin thickness, skin elasticity, skin conductance, and TEWL, and a reduction in the size of the corneocytes. No change in stratum corneum lipid content was observed. A sex-related difference was noted in the response to treatment under our experimental conditions, the female patients responding better. A punch biopsy (4 mm) was performed on both forearms of four patients after the 6-month period. Histologic and ultrastructural examination revealed epidermal and dermal changes evoking increased cellular metabolism in the retinoic acid-treated forearms.
- Published
- 1990
- Full Text
- View/download PDF
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