TY - JOUR
T1 - Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis vulgaris and predispose individuals to atopic dermatitis
AU - Sandilands, Aileen
AU - O'Regan, Grainne M.
AU - Liao, Haihui
AU - Zhao, Yiwei
AU - Terron-Kwiatkowski, Ana
AU - Watson, Rosemarie M.
AU - Cassidy, Andrew J.
AU - Goudie, David R.
AU - Smith, Frances J. D.
AU - McLean, W. H. Irwin
AU - Irvine, Alan D.
N1 - dc.publisher: Nature Publishing Group
Lead author involved in the overall strategy, planning, experimental work, analysis and writing of the first paper to describe less common mutations in filaggrin as the cause of ichthyosis vulgaris, a common skin scaling disease, as well as further genetic linkage evidence supporting the role of filaggrin mutations in eczema.
PY - 2006
Y1 - 2006
N2 - Mutations in the filament aggregating protein (filaggrin) gene have recently been identified as the cause of the common genetic skin disorder ichthyosis vulgaris (IV), the most prevalent inherited disorder of keratinization. The main characteristics of IV are fine-scale on the arms and legs, palmar hyperlinearity, and keratosis pilaris. Here, we have studied six Irish families with IV for mutations in filaggrin. We have identified a new mutation, 3702delG, in addition to further instances of the reported mutations R501X and 2282del4, which are common in people of European origin. A case of a 2282del4 homozygote was also identified. Mutation 3702delG terminates protein translation in filaggrin repeat domain 3, whereas both recurrent mutations occur in repeat 1. These mutations are semidominant: heterozygotes have an intermediate phenotype most readily identified by palmar hyperlinearity and in some cases fine-scale and/or keratosis pilaris, whereas homozygotes or compound heterozygotes generally have more marked ichthyosis. Interestingly, the phenotypes of individuals homozygous for R501X, 2282del4, or compound heterozygous for R501X and 3702delG, were comparable, suggesting that mutations located centrally in the filaggrin repeats are also pathogenic.
AB - Mutations in the filament aggregating protein (filaggrin) gene have recently been identified as the cause of the common genetic skin disorder ichthyosis vulgaris (IV), the most prevalent inherited disorder of keratinization. The main characteristics of IV are fine-scale on the arms and legs, palmar hyperlinearity, and keratosis pilaris. Here, we have studied six Irish families with IV for mutations in filaggrin. We have identified a new mutation, 3702delG, in addition to further instances of the reported mutations R501X and 2282del4, which are common in people of European origin. A case of a 2282del4 homozygote was also identified. Mutation 3702delG terminates protein translation in filaggrin repeat domain 3, whereas both recurrent mutations occur in repeat 1. These mutations are semidominant: heterozygotes have an intermediate phenotype most readily identified by palmar hyperlinearity and in some cases fine-scale and/or keratosis pilaris, whereas homozygotes or compound heterozygotes generally have more marked ichthyosis. Interestingly, the phenotypes of individuals homozygous for R501X, 2282del4, or compound heterozygous for R501X and 3702delG, were comparable, suggesting that mutations located centrally in the filaggrin repeats are also pathogenic.
U2 - 10.1038/sj.jid.5700459
DO - 10.1038/sj.jid.5700459
M3 - Article
C2 - 16810297
SN - 0022-202X
VL - 126
SP - 1770
EP - 1775
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 8
ER -