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Kindler syndrome: Extension of FERMT1 mutational spectrum and natural history
Author(s) -
Has Cristina,
Castiglia Daniele,
del Rio Marcela,
Garcia Diez Marta,
Piccinni Eugenia,
Kiritsi Dimitra,
Kohlhase Jürgen,
Itin Peter,
Martin Ludovic,
Fischer Judith,
Zambruno Giovanna,
BrucknerTuderman Leena
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21576
Subject(s) - biology , missense mutation , phenotype , genetics , disease , poikiloderma , natural history , mutation , loss function , gene , pathology , medicine , botany
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. Hum Mutat 32:1204–1212, 2011. ©2011 Wiley Periodicals, Inc.