{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T21:43:47Z","timestamp":1784324627481,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Atopic dermatitis is frequently associated with the onset of other allergic conditions, such as asthma, rhino-conjunctivitis and food allergy. The etiology of atopic dermatitis is marginally understood in spite of the number of predisposing factors, above all, mutations in the Filaggrin gene (FLG). In this study, the association between loss-of-function variants in the FLG gene and other allergic manifestations, in particular food allergy, was evaluated in an Italian pediatric population affected by atopic dermatitis. The 10 more frequently mutated loci in the FLG gene were genotyped in 238 children affected by atopic dermatitis and tested for association with clinical features of allergic disorders by a multivariate logistic regression model. R501X and 2282del4 were the only two mutations identified; 12.2% of children carry one of these variants, corresponding to an allelic frequency of 6.5%. According to multivariate statistical analysis, loss-of-function variants in the FLG gene represent a risk factor for the onset of severe manifestations of food allergy (OR = 8.9; CI: 3.1\u201328.3). Peanut and hazelnut were identified as high-risk foods in patients with FLG mutations. This study demonstrates that atopic children carrying FLG mutations represent a high-risk population due to their predisposition to develop severe food allergy reactions, such as anaphylaxis.<\/jats:p>","DOI":"10.3390\/jcm10020233","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T11:36:11Z","timestamp":1610364971000},"page":"233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2732-0747","authenticated-orcid":false,"given":"Annalisa","family":"Astolfi","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2229-5263","authenticated-orcid":false,"given":"Francesca","family":"Cipriani","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-3998","authenticated-orcid":false,"given":"Daria","family":"Messelodi","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"De Luca","sequence":"additional","affiliation":[{"name":"Giorgio Prodi Cancer Research Center, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8854-3821","authenticated-orcid":false,"given":"Valentina","family":"Indio","sequence":"additional","affiliation":[{"name":"Giorgio Prodi Cancer Research Center, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costanza","family":"Di Chiara","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8243-9727","authenticated-orcid":false,"given":"Arianna","family":"Giannetti","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, Division of Dermatology, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant\u2019Orsola-Malpighi, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iria","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, Division of Dermatology, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant\u2019Orsola-Malpighi, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Patrizi","sequence":"additional","affiliation":[{"name":"Dermatology\u2014IRCCS Policlinico di S.Orsola, Department of Experimental, Diagnostic and Speciality Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Ricci","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-9562","authenticated-orcid":false,"given":"Andrea","family":"Pession","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1067\/mai.2000.106484","article-title":"Atopic dermatitis: New insights and opportunities for therapeutic intervention","volume":"105","author":"Leung","year":"2000","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/all.12270","article-title":"New insights into the epidemiology of childhood atopic dermatitis","volume":"69","author":"Flohr","year":"2014","journal-title":"Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/ng1767","article-title":"Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis","volume":"38","author":"Palmer","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jaci.2006.05.004","article-title":"Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations","volume":"118","author":"Weidinger","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/sj.jid.5700587","article-title":"Null Mutations in the Filaggrin Gene (FLG) Determine Major Susceptibility to Early-Onset Atopic Dermatitis that Persists into Adulthood","volume":"127","author":"Barker","year":"2007","journal-title":"J. Investig. Derm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/pai.12025","article-title":"Food allergy and anaphylaxis in pediatrics: Update 2010\u20132012","volume":"23","author":"Santos","year":"2012","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1111\/j.1398-9995.2009.01952.x","article-title":"Food allergy and food sensitization in early childhood: Results from the DARC cohort","volume":"64","author":"Eller","year":"2009","journal-title":"Allergy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1476-7961-8-8","article-title":"Does improvement management of atopic dermatitis influence the appearance of respiratory allergic diseases? A follow-up study","volume":"8","author":"Ricci","year":"2010","journal-title":"Clin. Mol. Allergy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.jaci.2014.07.033","article-title":"Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence","volume":"134","author":"Venkataraman","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.jaci.2014.08.011","article-title":"Peanut allergy: Effect of environmental peanut exposure in children with filaggrin loss-of-function mutations","volume":"134","author":"Brough","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4168\/aair.2012.4.1.12","article-title":"Epidermal Barrier in Atopic Dermatitis","volume":"4","author":"Kim","year":"2012","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.anai.2016.03.027","article-title":"The clinical relevance of filaggrin mutations: Effect on allergic disease","volume":"117","author":"Tenn","year":"2016","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1111\/bjd.12969","article-title":"Filaggrin loss-of-function mutations and incident cancer: A population-based study","volume":"171","author":"Skaaby","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1111\/jdv.14172","article-title":"Filaggrin loss-of-function mutations, atopic dermatitis and risk of actinic keratosis: Results from two cross-sectional studies","volume":"31","author":"Andersen","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1111\/bjd.15747","article-title":"A randomized trial of a barrier lipid replacement strategy for the prevention of atopic dermatitis and allergic sensitization: The PEBBLES pilot study","volume":"178","author":"Lowe","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1824-7288-40-46","article-title":"Atopic dermatitis phenotypes in childhood","volume":"40","author":"Ricci","year":"2014","journal-title":"Ital. J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/all.12112","article-title":"Characterization of different courses of atopic dermatitis in adolescent and adult patients","volume":"68","author":"Garmhausen","year":"2013","journal-title":"Allergy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2340\/00015555924447","article-title":"Diagnostic Features of Atopic Dermatitis","volume":"92","author":"Hanifin","year":"1980","journal-title":"Acta Derm. Venereol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/S0190-9622(03)02539-8","article-title":"Consensus conference on pediatric atopic dermatitis","volume":"49","author":"Eichenfield","year":"2003","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000247298","article-title":"Severity Scoring of Atopic Dermatitis: The SCORAD Index","volume":"186","author":"Stalder","year":"1993","journal-title":"Dermatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1111\/pai.12016","article-title":"Oral food challenge: Safety, adherence to guidelines and predictive value of skin prick testing","volume":"23","author":"Calvani","year":"2012","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_22","unstructured":"(2016, March 16). ExAc Browser. Available online: http:\/\/exac.broadinstitute.org\/."},{"key":"ref_23","unstructured":"(2016, March 20). Primer Blast, Available online: https:\/\/www.ncbi.nlm.nih.gov\/tools\/primer-blast\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1111\/all.12429","article-title":"EAACI Food Allergy and Anaphylaxis Guidelines: Diagnosis and management of food allergy","volume":"69","author":"Muraro","year":"2014","journal-title":"Allergy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/bioinformatics\/19.1.149","article-title":"Genetic Power Calculator: Design of linkage and association genetic mapping studies of complex traits","volume":"19","author":"Purcell","year":"2003","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.jaci.2006.07.026","article-title":"Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march","volume":"118","author":"Marenholz","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/sj.jid.5700739","article-title":"Filaggrin mutations in children with severe atopic dermatitis","volume":"127","author":"Morar","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000109365","article-title":"R501X and 2282del4 Filaggrin Mutations Do Not Confer Susceptibility to Psoriasis and Atopic Dermatitis in Italian Patients","volume":"216","author":"Giardina","year":"2008","journal-title":"Dermatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1399-3038.2008.00808.x","article-title":"Association of Filaggrin loss-of-function-mutations with atopic dermatitis and asthma in the Early Treatment of the Atopic Child (ETAC) population","volume":"20","author":"Marenholz","year":"2009","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_30","first-page":"128","article-title":"The prevalence of mutations in the gene encoding filaggrin in the population of Polish patients with atopic dermatitis","volume":"33","author":"Czajkowski","year":"2016","journal-title":"Postep. Dermatol. Alergol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.5114\/pdia.2015.48036","article-title":"The frequency of polymorphic variants of filaggrin gene and clinical atopic dermatitis","volume":"1","author":"Bozek","year":"2016","journal-title":"Adv. Dermatol. Allergol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/pde.14025","article-title":"Prevalence of FLG loss-of-function mutations R501X, 2282del4, and R2447X in Spanish children with atopic dermatitis","volume":"37","author":"Lorente","year":"2020","journal-title":"Pediatr. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/all.12569","article-title":"Loss-of-function variants of the filaggrin gene are associated with clinical reactivity to foods","volume":"70","author":"Kollen","year":"2015","journal-title":"Allergy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.jaci.2011.01.031","article-title":"Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy","volume":"127","author":"Brown","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jaci.2014.10.007","article-title":"Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy","volume":"135","author":"Brough","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1016\/j.jaci.2017.05.034","article-title":"Association study of childhood food allergy with genome-wide association studies\u2013discovered loci of atopic dermatitis and eosinophilic esophagitis","volume":"140","author":"Hirota","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/s41467-017-01220-0","article-title":"Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy","volume":"8","author":"Marenholz","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eaav2685","DOI":"10.1126\/scitranslmed.aav2685","article-title":"The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype","volume":"11","author":"Leung","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jaci.2012.09.015","article-title":"Identifying infants at high risk of peanut allergy: The Learning Early About Peanut Allergy (LEAP) screening study","volume":"131","author":"Roberts","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/j.1365-2222.2005.02260.x","article-title":"Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization","volume":"35","author":"Strid","year":"2005","journal-title":"Clin. Exp. Allergy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.jaci.2014.07.032","article-title":"Dry roasting enhances peanut-induced allergic sensitization across mucosal and cutaneous routes in mice","volume":"134","author":"Moghaddam","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jaci.2013.03.043","article-title":"Filaggrin gene mutation associations with peanut allergy persist despite variations in peanut allergy diagnostic criteria or asthma status","volume":"132","author":"Asai","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.anai.2017.11.023","article-title":"The skin as a target for prevention of the atopic march","volume":"120","author":"Lowe","year":"2018","journal-title":"Ann. Allergy Asthma Immunol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/2\/233\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:09:34Z","timestamp":1760159374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/2\/233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["jcm10020233"],"URL":"https:\/\/doi.org\/10.3390\/jcm10020233","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]}}}