title: Novel filaggrin mutation but no other loss-of-function variants found in Ethiopian patients with atopic dermatitis.
abstract: BACKGROUND
  Filaggrin is a key protein involved in maintaining skin barrier function and hydration. Mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and are a major predisposing factor for atopic dermatitis (AD) in individuals of European and Asian descent. It has been proposed that FLG mutations are population specific and a difference in the spectra of mutations between different ancestral groups has been described. However, it is unknown whether FLG mutations in the African population are a causative genetic factor for IV and predispose to AD, or whether other mechanisms are more prominent.
  
  
  OBJECTIVE
  The present aim was to investigate the role of FLG mutations as predisposing factors for IV or AD among individuals from Ethiopia.
  
  
  METHODS
  A case series of Ethiopian patients with AD (n = 103) and IV (n = 7) together with controls (n = 103; subjects without past or present history of AD, dry skin or atopic manifestations) was collected at the outpatient dermatology clinics at ALERT Dermatology Hospital, Tikur Anbessa Hospital and Gondar University Hospital, Ethiopia. AD was diagnosed by a dermatologist using the U.K. Working Party's diagnostic criteria. The IV diagnosis was based on clinical examination and genetic testing of the steroid sulphatase gene to exclude X-linked recessive ichthyosis. Patients were studied with direct sequencing (n = 40) and/or allelic discrimination (n = 110). Immunohistochemical analysis was performed for filaggrin expression in the skin of patients (n = 7) and controls (n = 2).
  
  
  RESULTS
  The Ethiopian patients and controls were genotyped for the four previously described common European FLG null mutations (R501X, 2282del4, S3247X, R2447X) and no carriers were found. In one patient with AD a novel heterozygous 2-bp deletion, 632del2, leading to a premature stop codon was revealed by direct sequencing. No additional carrier of this deletion or other mutations was found. In addition, no difference in filaggrin expression was detected in AD or IV skin compared with healthy control skin.
  
  
  CONCLUSIONS
  Our results indicate that FLG loss-of-function-variants are less common in patients with IV and AD in the Ethiopian population, suggesting that other factors may be of importance in the pathogenesis in this ethnic group.
authors.affiliation: Dermatology Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. marten.winge@ki.se
authors.forename: M C G
authors.initials: MC
authors.lastname: Winge
authors.forename: K D
authors.initials: KD
authors.lastname: Bilcha
authors.forename: A
authors.initials: A
authors.lastname: Liedén
authors.forename: D
authors.initials: D
authors.lastname: Shibeshi
authors.forename: A
authors.initials: A
authors.lastname: Sandilands
authors.forename: C-F
authors.initials: CF
authors.lastname: Wahlgren
authors.forename: W H I
authors.initials: WH
authors.lastname: McLean
authors.forename: M
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: M
authors.initials: M
authors.lastname: Bradley
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D005002:Ethiopia / Q000208:ethnology; D005260:Female; D000091344:Filaggrin Proteins; D006579:Heterozygote; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000235:genetics* / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D007150:Immunohistochemistry; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012867:Skin / Q000378:metabolism; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007073:Immunoglobulin E