title: Kindler syndrome: extension of FERMT1 mutational spectrum and natural history.
abstract: 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.
authors.affiliation: Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Has
authors.forename: Daniele
authors.initials: D
authors.lastname: Castiglia
authors.forename: Marcela
authors.initials: M
authors.lastname: del Rio
authors.forename: Marta Garcia
authors.initials: MG
authors.lastname: Diez
authors.forename: Eugenia
authors.initials: E
authors.lastname: Piccinni
authors.forename: Dimitra
authors.initials: D
authors.lastname: Kiritsi
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kohlhase
authors.forename: Peter
authors.initials: P
authors.lastname: Itin
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
mesh_terms: D000293:Adolescent; D000328:Adult; D001768:Blister / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004820:Epidermolysis Bullosa / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010510:Periodontal Diseases / Q000235:genetics*; D010641:Phenotype; D010787:Photosensitivity Disorders / Q000235:genetics*
chemical_list: C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins