Details

Autor(en) / Beteiligte

• Wong, X.F. Colin C.
• Denil, Simon L.I.J.
• Foo, Jia Nee
• Chen, Huijia
• Tay, Angeline Su Ling
• Haines, Rebecca L.
• Tang, Mark B.Y.
• McLean, W.H. Irwin
• Sandilands, Aileen
• Smith, Frances J.D.
• Lane, E. Birgitte
• Liu, Jianjun
• Common, John E.A.

Titel

Array-based sequencing of filaggrin gene for comprehensive detection of disease-associated variants

Ist Teil von

• Journal of allergy and clinical immunology, 2018-02, Vol.141 (2), p.814-816

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• FLG loss-of-function (LoF) variants are associated with ichthyosis vulgaris and the major genetic risk factor for developing atopic dermatitis (AD).1-3 Genetic stratification of patients with AD according to FLG LoF risk is a common practice for both research and clinical studies; however, few studies comprehensively sequence the entire FLG coding region. The combined FLG LoF mutation allele frequency for Chinese Singaporean patients with AD is now 32.3%, an increase from 20.2% in our previous survey of 425 patient samples further supporting the biological importance of FLG mutations in AD.7 Smaller cohorts of 19 Indian and 36 Malay patients were analyzed and we identified FLG LoF variants in 9 Indian samples and 9 Malay samples (see Fig 1, D; see Tables E6 and E7 in this article's Online Repository at www.jacionline.org). [...]we describe a multiplexed targeted resequencing method to study the FLG coding region. Supplementary data Table I Concordance of FLG LoF variant detection for 14 previously fully Sanger-sequenced AD samples using our MiSeq 2x250 bp protocol Sample ID Sanger sequencing Illumina MiSeq assay IA-P003 p.S1515X p.S1515X IA-P009 No LoF detected No LoF detected IA-P014 No LoF detected No LoF detected IA-P017 p.E2422X p.E2422X IA-P021 p.S406X; c.6950_6957del8 p.S406X; c.6950_6957del8 IA-P024 c.1640delG c.1640delG IA-P025 p.Q368X; c.3321delA p.Q368X; c.3321delA IA-P028 c.7945delA c.7945delA IA-P062 p.Q2417X p.Q2417X IA-P063 c.2952delC c.2952delC IA-P083∗ c.9040_9058dup19 c.9040_9058dup19; p.Q1790X IA-P084∗ p.S1302X p.S1302X; p.S1515X IA-P090 c.4004del2 c.4004del2 IA-P094 c.2282del4; p.R2447X c.2282del4; p.R2447X 1 C.N.A. Palmer, A.D. Irvine, A. Terron-Kwiatkowski, Y. Zhao, H. Liao, S.P. Lee, Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis, Nat Genet, Vol. 38, 2006, 441-446 2 F.J.D. Smith, A.D. Irvine, A. Terron-Kwiatkowski, A. Sandilands, L.E. Campbell, Y. Zhao, Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris, Nat Genet, Vol. 38, 2006, 337-342 3 R.A.H.M. van den Oord, A. Sheikh, Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and meta-analysis, BMJ, Vol. 339, 2009, b2433 4 A.G. Clark, M.J. Hubisz, C.D. Bustamante, S.H. Williamson, R. Nielsen, Ascertainment bias in studies of human genome-wide polymorphism, Genome Res, Vol. 15, 2005, 1496-1502 5 A. Sandilands, A. Terron-Kwiatkowski, P.R. Hull, T.H. Clayton, R.M. Watson, Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema, Nat Genet, Vol. 39, 2007, 650-654 6 A.D. Irvine, W.H.I. McLean, D.Y.M. Leung, Filaggrin mutations associated with skin and allergic diseases, N Engl J Med, Vol. 365, 2011, 1315-1327 7 H. Chen, J.E.A. Common, R.L. Haines, A. Balakrishnan, S.J. Brown, C.S.M. Goh, Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations, Br J Dermatol, Vol. 165, 2011, 106-114 8 S.J. Brown, K. Kroboth, A. Sandilands, L.E. Campbell, E. Pohler, S. Kezic, Intragenic copy number variation within filaggrin contributes to the risk of atopic dermatitis with a dose-dependent effect, J Invest Dermatol, Vol. 132, 2012, 98-104