['Filaggrin is a key protein involved in skin barrier function. Filaggrin (FLG) null mutations are important genetic predisposing factors for atopic disease.', 'To study the role of FLG null alleles in the clinical phenotype in children and young adults with asthma.', 'FLG mutations R501X and 2282del4 were assayed in 874 subjects 3 to 22 years old with asthma from Tayside. Lung function and disease severity were also studied.', 'The filaggrin mutations were significantly associated with greater disease severity for asthma. Independent of eczema, mean FEV(1)/forced vital capacity of FLG wild-type individuals differed from those carrying either FLG null allele (0.89 vs 0.86; P = .012). Individuals bearing FLG null alleles were more likely to be prescribed increased medication (chi(2) = 10.3; P = .001), with the homozygote null individuals having an odds ratio of 6.68 (95% CI, 1.7-27.0; P = .008) for being prescribed long-acting beta-agonists in addition to inhaled steroids. FLG null alleles were also associated with increased rescue medication use (P = .004). Individuals with asthma and with FLG null alleles were more likely to have eczema, and individuals with eczema tended to have more severe asthma; however, the association of FLG null alleles with all markers of asthma disease severity was similar in children with and without eczema.'] Are filaggrin null mutations associated with increased asthma severity in children and young adults?