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. OBJECTIVES: 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.
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. OBJECTIVES: 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: Robert Gruber; Jeffrey L Sugarman; Debra Crumrine; Melanie Hupe; Theodora M Mauro; Elizabeth A Mauldin; Jacob P Thyssen; Johanna M Brandner; Hans-Christian Hennies; Matthias Schmuth; Peter M Elias Journal: Am J Pathol Date: 2015-02-07 Impact factor: 4.307
Authors: Gabriela Queila de Carvalho-Siqueira; Galina Ananina; Bruno Batista de Souza; Murilo Guimarães Borges; Mirta Tomie Ito; Sueli Matilde da Silva-Costa; Igor de Farias Domingos; Diego Arruda Falcão; Iscia Lopes-Cendes; Marcos André Cavalcanti Bezerra; Aderson da Silva Araújo; Antônio Roberto Lucena-Araújo; Marilda de Souza Gonçalves; Sara Teresinha Olalla Saad; Fernando Ferreira Costa; Mônica Barbosa de Melo Journal: Exp Biol Med (Maywood) Date: 2019-05-12
Authors: David J Margolis; Nandita Mitra; Heather Gochnauer; Bradley Wubbenhorst; Kurt D'Andrea; Adam Kraya; Ole Hoffstad; Jayanta Gupta; Brian Kim; Albert Yan; Zelma Chiesa Fuxench; Katherine L Nathanson Journal: J Invest Dermatol Date: 2018-02-08 Impact factor: 8.551
Authors: Yuhree Kim; Maria Blomberg; Sheryl L Rifas-Shiman; Carlos A Camargo; Diane R Gold; Jacob P Thyssen; Augusto A Litonjua; Emily Oken; Maryam M Asgari Journal: J Invest Dermatol Date: 2018-11-08 Impact factor: 8.551