BACKGROUND: Filaggrin is a key protein involved in skin barrier function. Recently, mutations in the filaggrin gene, FLG, were identified in European families with ichthyosis vulgaris (IV) and shown to be an important predisposing factor for atopic dermatitis (AD). OBJECTIVE: To study the role of FLG mutations in IV/AD in Japan. METHODS: The known filaggrin mutations were studied by genotyping and new mutations identified by DNA sequencing. RESULTS: The European-specific mutations R501X and 2282del4 were absent from 253 Japanese individuals. We therefore sequenced the FLG gene in 4 Japanese families with IV and identified 2 novel mutations, 3321delA and S2554X. Immunohistologic and ultrastructural observations indicated that both truncation mutations lead to a striking reduction of keratohyalin granules in the epidermis. We screened 143 Japanese patients with AD for these FLG null mutations and identified them in 8 patients with AD (5.6%), including S2554X in 6 patients (4.2%) and 3321delA in 2 patients (1.4%). Both null variants were absent from 156 unrelated Japanese nonatopic and nonichthyotic controls, giving a significant statistical association between the FLG mutations and AD (chi(2)P value, .0015). This is the first report of FLG mutations in a non-European population. CONCLUSION: Our data indicate that FLG mutations in Japan are unique from those found in European-origin populations. CLINICAL IMPLICATIONS: Filaggrin null variants are also significant predisposing factors for AD in Japan and, on the basis of the recent European studies, may predict a more severe and persistent form of atopy.
BACKGROUND: Filaggrin is a key protein involved in skin barrier function. Recently, mutations in the filaggrin gene, FLG, were identified in European families with ichthyosis vulgaris (IV) and shown to be an important predisposing factor for atopic dermatitis (AD). OBJECTIVE: To study the role of FLG mutations in IV/AD in Japan. METHODS: The known filaggrin mutations were studied by genotyping and new mutations identified by DNA sequencing. RESULTS: The European-specific mutations R501X and 2282del4 were absent from 253 Japanese individuals. We therefore sequenced the FLG gene in 4 Japanese families with IV and identified 2 novel mutations, 3321delA and S2554X. Immunohistologic and ultrastructural observations indicated that both truncation mutations lead to a striking reduction of keratohyalin granules in the epidermis. We screened 143 Japanese patients with AD for these FLG null mutations and identified them in 8 patients with AD (5.6%), including S2554X in 6 patients (4.2%) and 3321delA in 2 patients (1.4%). Both null variants were absent from 156 unrelated Japanese nonatopic and nonichthyotic controls, giving a significant statistical association between the FLG mutations and AD (chi(2)P value, .0015). This is the first report of FLG mutations in a non-European population. CONCLUSION: Our data indicate that FLG mutations in Japan are unique from those found in European-origin populations. CLINICAL IMPLICATIONS: Filaggrin null variants are also significant predisposing factors for AD in Japan and, on the basis of the recent European studies, may predict a more severe and persistent form of atopy.
Authors: Jorge Esparza-Gordillo; Stephan Weidinger; Regina Fölster-Holst; Anja Bauerfeind; Franz Ruschendorf; Giannino Patone; Klaus Rohde; Ingo Marenholz; Florian Schulz; Tamara Kerscher; Norbert Hubner; Ulrich Wahn; Stefan Schreiber; Andre Franke; Rainer Vogler; Simon Heath; Hansjörg Baurecht; Natalija Novak; Elke Rodriguez; Thomas Illig; Min-Ae Lee-Kirsch; Andrzej Ciechanowicz; Michael Kurek; Tereza Piskackova; Milan Macek; Young-Ae Lee; Andreas Ruether Journal: Nat Genet Date: 2009-04-06 Impact factor: 38.330
Authors: Shona Hiedi Wood; Xiayi Ke; Tim Nuttall; Neil McEwan; William E Ollier; Stuart D Carter Journal: Immunogenetics Date: 2010-01-05 Impact factor: 2.846