Exome sequencing of Filaggrin and related genes in African-American children with atopic dermatitis

Atopic dermatitis (AD) is a common chronic relapsing disease. There is a considerable body of evidence supporting a genetic basis for AD (Bussman et al., 2011;Ellinghaus et al., 2013). Mutations in the Filaggrin (FLG) gene have been consistently found to be associated with AD in people of European and Asian ancestry (Brown and McLean, 2012). More than 40 FLG loss-of-function mutations have been described in Europeans and Asians, (Brown and McLean, 2012).However, FLG loss-of-function mutations have not commonly been found in Africans or African-Americans (Margolis et al., 2012;Brown and McLean, 2012;Winge et al., 2011a). Loss-of-function mutations in exon 3 of FLG result in diminished or absent filaggrin protein, most often due to a premature stop codon or a frameshift mutation resulting in a stop codon further downstream. Interestingly, the absence of profilaggrin protein (precursor of filaggrin) has also been noted in keratohyalin granules in the majority of those with ichthyosis vulgaris (IV) of European and Asian ancestry (Perusquia-Ortiz.A.M. et al., 2013;Thyssen et al., 2013;Fleckman and Brumbaugh, 2002).