Filaggrin mutations are genetic modifying factors exacerbating X-linked ichthyosis.
Mutations inactivating the STS gene cause X-linked ichthyosis (XLI), whereas null mutations in the FLG gene cause ichthyosis vulgaris. Two brothers presented with XLI. One had a typical fine scaling, and the other was much more severely affected. Both patients carried STS missense mutation T165I. Furthermore, the more severely affected patient also carried heterozygous FLG mutation R501X, which was absent from his mildly affected brother. These data suggest that disrupting epidermal differentiation via different pathways can increase phenotypic severity. Owing to the high population frequency of FLG mutations, filaggrin is a possible genetic modifier in other genodermatoses.
Liao
Haihui
H
Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Waters
Alex J
AJ
Goudie
David R
DR
Aitken
David A
DA
Graham
Gordon
G
Smith
Frances J D
FJ
Lewis-Jones
Sue
S
McLean
W H Irwin
WH
D001483:Base Sequence; D002454:Cell Differentiation; D002648:Child; D004817:Epidermis / Q000378:metabolism; D005192:Family Health; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D016114:Ichthyosis, X-Linked / Q000235:genetics*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins