Prevalence of FLG loss‐of‐function mutations R501X, 2282del4, and R2447X in Spanish children with atopic dermatitis

González‐Tarancón, Ricardo; Sanmartín, Rosalia; Lorente, Fabiola; Salvador-Rupérez, Elvira; Hernández‐Martín, Ángela; Rello, Luis; Puzo, José; Gilaberte, Yolanda

doi:10.1111/pde.14025

Cited by 15 publications

(12 citation statements)

References 20 publications

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“…Most of the patients experienced the beginning of the disease at early infancy, after the 3rd month of life. In the group of patients with very early onset (0–3 years), we had 72% of patients; early onset (3–5 years), 9% of patients; childhood (5–18 years), 15% of patients; and adult‐onset, 4% patients. There were no patients with late onset of the disease (>40 years; Table ).…”

Section: Resultsmentioning

confidence: 99%

“…The most prevalent FLG mutation in AD patients was R501X (9.9%), followed by R2447X (2.7%) and 2282del4 (1.8%). 37 Another study that included Greek and Egyptian 162 AD patients reported the absence of known null mutations (501X and 2282del4 mutations) and the sequence analysis revealed 2 unknown null mutations only in 2 Egyptian patients, suggesting a low frequency of FLG null mutations in Greek and Egyptian populations. 38 The reason for such a large variability of the prevalence of FLG mutations is still under debate.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent Spanish study, the combined mutation frequency was 1.9% in the control group and 12.6% in the AD group. The most prevalent FLG mutation in AD patients was R501X (9.9%), followed by R2447X (2.7%) and 2282del4 (1.8%) …”

Section: Discussionmentioning

confidence: 99%

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Filaggrin loss‐of‐function mutations and levels of filaggrin degradation products in adult patients with atopic dermatitis in Croatia

Tončić

Kežić

Jakaša

et al. 2020

Acad Dermatol Venereol

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Background FLG loss-of-function mutations (FLG LOF) represent the strongest genetic risk factor for atopic dermatitis (AD) and are associated with early-onset and more severe disease. The prevalence of FLG mutations varies greatly across Europe. At present, there are no data on FLG mutation prevalence in Croatian AD patients. Objectives To investigate the prevalence of FLG LOF mutations in adult patients with AD and healthy controls. Next to measure the stratum corneum (SC) levels of filaggrin degradation products (NMF), transepidermal water loss (TEWL) and pH in lesional and non-lesional skin. Methods We recruited 100 AD patients with moderate to severe disease and 50 healthy controls. They were screened for three FLG mutations (R501X, 2282del4 and R2447X). Samples of the SC for NMF analysis were collected by adhesive tapes. TEWL and skin surface pH levels were determined on the lesional and non-lesional skin. Results The combined mutation frequency was 4% in the AD group, and all patients with FLG mutations were homozygous carriers. In the control group, no mutations were found. The most common FLG mutation in AD patients was 2282del4 (3%), followed by R501X (1%). As compared to healthy controls, NMF values were strongly reduced in lesional skin; however, no significant difference was found for non-lesional skin. AD patients had elevated TEWL in both lesional and non-lesional skin. The same pattern was observed for pH. Conclusions Our study expands understanding of the landscape of FLG mutations in the European population. The low frequency of FLG mutations and similar levels of filaggrin degradation products in healthy controls and in non-lesional skin of AD patients suggest that filaggrin deficiency does not confer a major risk for AD in the Croatian population.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Filaggrin loss‐of‐function mutations and levels of filaggrin degradation products in adult patients with atopic dermatitis in Croatia

Tončić

Kežić

Jakaša

et al. 2020

Acad Dermatol Venereol

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“…In the European population, the prevalence of FLG gene alterations, especially of R501X and 2282del4 mutations, varies among different regions, depending on the ethnic groups [3][4][5][26][27][28][29][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis

Astolfi

Cipriani

Messelodi

et al. 2021

JCM

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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: 3.1–28.3). 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.

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“…A very recent Spanish study, performed on 111 AD patients and 103 controls, searching for three FLG null mutations (R501X, 2282del4, and R2447X) found that combined mutation incidence was 1.9% in the healthy group and 12.6% in the AD group, and thus 9.9% R501X, 2.7% R2447X and 1.8% 2282del4, respectively ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Mutations of filament‑aggregating protein gene in Romanian children diagnosed with atopic dermatitis

Chiriac¹,

Popescu

Butnariu

et al. 2020

Exp Ther Med

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Association of atopic dermatitis (AD) and several mutations of various genes of the immune system, in particular filament-aggregating protein gene (FLG) has been investigated in many studies. The association between defective FLG and AD in the Romanian population has not been assessed or published. The present study focused on the genetic background of AD, aiming to assess the prevalence of FLG mutations in Romanian patients with AD. Genetic background of AD was tested for common FLG-mutations: R501X, 2282del4, S3247X and R2447X. The study involved 48 Romanian Caucasian children aged between two months and six years diagnosed with AD, and 48 healthy volunteers; DNA extraction involved 50% of the patients to give samples by using buccal swabs and 50% by collection of whole blood samples. Genetic predisposition was evaluated based on family history, atopy history and profilaggrin genotyping. DNA extracted from blood samples was adequate to study FLG mutations, although no mutation was identified. Genetic factors do not have a unique critical role in AD; therefore, environmental factors unquestionably play an important role in this disease, but the clear-cut part that these factors trigger toward increasing the risk of AD in childhood is still obscure.

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Prevalence of FLG loss‐of‐function mutations R501X, 2282del4, and R2447X in Spanish children with atopic dermatitis

Cited by 15 publications

References 20 publications

Filaggrin loss‐of‐function mutations and levels of filaggrin degradation products in adult patients with atopic dermatitis in Croatia

Filaggrin loss‐of‐function mutations and levels of filaggrin degradation products in adult patients with atopic dermatitis in Croatia

Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis

Mutations of filament‑aggregating protein gene in Romanian children diagnosed with atopic dermatitis

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