Long-term follow-up of patients with recessive dystrophic epidermolysis bullosa in the Netherlands

Autor: Hendri H. Pas, Robert M.W. Hofstra, Miranda Nijenhuis, Peter C. van den Akker, Marcel F. Jonkman, Hans Scheffer, Anthonie J. van Essen, Rowdy Meijer, Gonnie Meijer, Marian M.J. Kraak
Přispěvatelé: Translational Immunology Groningen (TRIGR)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Male
Pathology
Recessive dystrophic epidermolysis bullosa
Neuroinformatics [DCN 3]
medicine.disease_cause
Biochemistry
DOMAIN
Genotype
COL7A1
Child
Netherlands
Mutation
MESSENGER-RNA DECAY
Exons
REVERTANT MOSAICISM
Middle Aged
Phenotype
ANCHORING FIBRILS
Epidermolysis Bullosa Dystrophica
Pedigree
NONSENSE
Child
Preschool
Type VII collagen
DISEASE SEVERITY
Female
Mechanobullous skin disease
Adult
medicine.medical_specialty
Collagen Type VII
Adolescent
Genes
Recessive
Phenotype-genotype correlations
Dermatology
Biology
Genomic disorders and inherited multi-system disorders [IGMD 3]
Young Adult
COL7A1 MUTATION
Microscopy
Electron
Transmission
Anchoring fibrils
VII COLLAGEN GENE
medicine
Humans
Genetic Predisposition to Disease
Molecular Biology
Gene
Aged
EXONIC SPLICING ENHANCERS
Infant
Immunostaining
SKIN
Follow-Up Studies
Zdroj: Journal of Dermatological Science, 56, 9-18
Journal of Dermatological Science, 56, 1, pp. 9-18
Journal of dermatological science, 56(1), 9-18
ISSN: 0923-1811
Popis: Background: The current classification of recessive dystrophic epidermolysis bullosa (RDEB) comprises two major subtypes: 'severe generalized RDEB'(RDEB-sev gen) with early-onset, extensive, generalized blistering and scarring, complete absence of type VII Collagen, and bi-allelic COL7A1 null mutations; milder 'generalized other RDEB' (RDEB-O) with reduced-to-normal type VII Collagen expression, and non-null genotypes.Objective: To search for previously unrecognized phenotype-genotype correlations in 33 Dutch RDEB families.Methods: We analyzed extensive clinical follow-up data, available for all patients up to 19 years, detailed type VII Collagen immunostaining and genotypes, and correlated clinical phenotype to molecular phenotype and genotype.Results: We identified 20 novel COL7A1 mutations. In 14 of 15 RDEB-sev gen patients type VII Collagen was completely absent, one had strongly reduced type VII Collagen, and all carried bi-allelic null mutations. Five of 11 RDEB-O patients developed pseudosyndactyly of the fingers preceded by skin atrophy and flexion contractures later in childhood and adolescence. All five had esophageal involvement and growth retardation. Type VII collagen immunostaining ranged from strongly reduced to slightly reduced in RDEB-O patients with pseudosyndactyly, whereas RDEB-O patients without pseudosyndactyly had slightly reduced to normal type VII Collagen staining. There was no difference in genotypes between both groups, although we unexpectedly found bi-allelic null mutations in two of five RDEB-O patients with pseudosyndactyly.Conclusion: Pseudosyndactyly occurs in approximately half of RDEB-O patients when type VII Collagen is strongly reduced. The prognosis in RDEB cannot always be simply predicted from the COL7A1 genotype. (C) 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Databáze: OpenAIRE
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