Kindler syndrome: extension of FERMT1 mutational spectrum and natural history
| Autor: | Eugenia Piccinni, Giovanna Zambruno, Leena Bruckner-Tuderman, Cristina Has, Peter Itin, Marcela Del Rio, Dimitra Kiritsi, Ludovic Martin, Judith Fischer, Jürgen Kohlhase, Daniele Castiglia, Marta Garcia Diez |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Adolescent Medicina Mutation Missense Poikiloderma Disease Biology Bioinformatics medicine.disease_cause Kindler syndrome Blister Genetics medicine Humans Missense mutation Photosensitivity Disorders Epidermolysis bullosa Kindlin Gene mutation Child FERMT1 Genetic Association Studies Periodontal Diseases Genetics (clinical) Mutation Fermitin Membrane Proteins medicine.disease Phenotype Neoplasm Proteins Child Preschool Skin cancer Epidermolysis Bullosa |
| Zdroj: | e-Archivo. Repositorio Institucional de la Universidad Carlos III de Madrid instname |
| Popis: | Mutations in the FERMT1 gene (also known as KIND1), encoding the focal adhesion protein kindlin-1, underlie the Kindler syndrome (KS), an autosomal recessive skin disorder with an intriguing progressive phenotype comprising skin blistering, photosensitivity, progressive poikiloderma with extensive skin atrophy, and propensity to skin cancer. Herein we review the clinical and genetic data of 62 patients, and delineate the natural history of the disorder, for example, age at onset of symptoms, or risk of malignancy. Although most mutations are predicted to lead to premature termination of translation, and to loss of kindlin-1 function, significant clinical variability is observed among patients. There is an association of FERMT1 missense and in-frame deletion mutations with milder disease phenotypes, and later onset of complications. Nevertheless, the clinical variability is not fully explained by genotype-phenotype correlations. Environmental factors and yet unidentified modifiers may play a role. Better understanding of the molecular pathogenesis of KS should enable the development of prevention strategies for disease complications. Contract grant sponsors: International Kindler Syndrome; The German Federal Ministry for Education and Research; The Excellence Initiative of the German federal and stage government and Freiburg Institute for Advanced Studies, School of Life Sciences (to L.B.T); The Italian Ministry of Heath |
| Databáze: | OpenAIRE |
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