Improving the diagnostic yield for filaggrin: Concealed mutations in the Dutch population

Leersum, Frank S van; Nagtzaam, Ivo F.; Oosterhoud, C.N. van; Ghesquiere, Stijn; Brandts, Roel; Gostyński, Antoni; Steijlen, P.M.; Geel, Michel van

doi:10.1016/j.jaci.2020.01.033

Cited by 9 publications

(15 citation statements)

References 14 publications

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“…Clinically, SICI should be distinguished from ichthyosis vulgaris by the disease onset and course. However, from a genetic point of view, ARCI diagnostic may be combined with a complete FLG mutation analysis 20 …”

Section: Discussionmentioning

confidence: 99%

Quality of life and clinical characteristics of self‐improving congenital ichthyosis within the disease spectrum of autosomal‐recessive congenital ichthyosis

Hake

Süßmuth

Komlósi

et al. 2022

Acad Dermatol Venereol

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Background Autosomal‐recessive congenital ichthyosis (ARCI) is a heterogeneous group of ichthyoses presenting at birth. Self‐improving congenital ichthyosis (SICI) is a subtype of ARCI and is diagnosed when skin condition improves remarkably (within years) after birth. So far, there are sparse data on SICI and quality of life (QoL) in this ARCI subtype. This study aims to further delineate the clinical spectrum of SICI as a rather unique subtype of ARCI. Objectives This prospective study included 78 patients (median age: 15 years) with ARCI who were subdivided in SICI (n = 18) and non‐SICI patients (nSICI, n = 60) by their ARCI phenotype. Methods Quality of life (QoL) was assessed using the (Children’s) Dermatology Life Quality Index. Statistical analysis was performed with chi‐squared and t‐Tests. Results The genetically confirmed SICI patients presented causative mutations in the following genes: ALOXE3 (8/16; 50.0%), ALOX12B (6/16; 37.5%), PNPLA1 (1/16; 6.3%) and CYP4F22 (1/16; 6.3%). Hypo‐/anhidrosis and insufficient vitamin D levels (<30 ng/mL) were often seen in SICI patients. Brachydactyly (a shortening of the 4th and 5th fingers) was statistically more frequent in SICI (P = 0.023) than in nSICI patients. A kink of the ear’s helix was seen in half of the SICI patients and tends to occur more frequently in patients with ALOX12B mutations (P = 0.005). QoL was less impaired in patients under the age of 16, regardless of ARCI type. Conclusions SICI is an underestimated, milder clinical variant of ARCI including distinct features such as brachydactyly and kinking of the ears. Clinical experts should be aware of these features when seeing neonates with a collodion membrane. SICI patients should be regularly checked for clinical parameters such as hypo‐/anhidrosis or vitamin D levels and monitored for changes in quality of life.

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Section: Discussionmentioning

confidence: 99%

Quality of life and clinical characteristics of self‐improving congenital ichthyosis within the disease spectrum of autosomal‐recessive congenital ichthyosis

Hake

Süßmuth

Komlósi

et al. 2022

Acad Dermatol Venereol

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“…Although the choice for including the most common FLG mutations in European populations is in line with previous studies, 11,12 other less frequent FLG mutations could exist in low numbers since up to 113 FLG mutations resulting in premature protein termination have been described. A recent study including patients with AD and ichthyosis vulgaris (IV) showed that screening the entire encoding region of FLG for mutations led to an improvement of the diagnostic yield 34 . As this is the first study in a general cohort addressing the association between FLG mutation and immune cell numbers, future studies are needed for validation of our results.…”

Section: Discussionmentioning

confidence: 72%

“…23,24 Second, the AD population for the subset analyses was relatively small which could showed that screening the entire encoding region of FLG for mutations led to an improvement of the diagnostic yield. 34 As this is the first study in a general cohort addressing the association between FLG mutation and immune cell numbers, future studies are needed for validation of our results.…”

Section: Methodological Considerationsmentioning

confidence: 82%

Increased Th22 cell numbers in a general pediatric population with filaggrin haploinsufficiency: The Generation R Study

Looman

Mierlo

Zelm

et al. 2021

Pediatric Allergy Immunology

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“…This was necessary to ascertain FLG null status by screening the four mutations which are most prevalent in the white European population and further work is required in populations of other ethnicities. More detailed FLG analysis, for example, using optimized methods of next-generation sequencing to fully sequence the gene, 19 might be useful to ascertain the full burden of FLG null mutations and this might improve predictive value. However, it would also preclude current routine clinical use.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Clinical examination for hyperlinear palms to determine filaggrin genotype: A diagnostic test accuracy study

Bradshaw

Haines

Kim

et al. 2021

Clin Experimental Allergy

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Background: Observational studies have reported an association between allergic disease and mental health, but a causal relationship has not been established. Here, we use Mendelian randomization (MR) to investigate a possible causal relationship between atopic disease and mental health phenotypes. Methods:The observational relationship between allergic disease and mental health was investigated in UK Biobank. The direction of causality was investigated with bidirectional two-sample MR using summary-level data from published genome-wide association studies. A genetic instrument was derived from associated variants for a broad allergic disease phenotype to test for causal relationships with various mental health outcomes. We also investigated whether these relationships were specific to atopic dermatitis (AD), asthma or hayfever. Given the multiple testing burden, we applied a Bonferroni correction to use an individual test p-value threshold of .0016 (32 tests). Results:We found strong evidence of an observational association between the broad allergic disease phenotype and depression (OR self-report =1.45,

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Improving the diagnostic yield for filaggrin: Concealed mutations in the Dutch population

Cited by 9 publications

References 14 publications

Quality of life and clinical characteristics of self‐improving congenital ichthyosis within the disease spectrum of autosomal‐recessive congenital ichthyosis

Quality of life and clinical characteristics of self‐improving congenital ichthyosis within the disease spectrum of autosomal‐recessive congenital ichthyosis

Increased Th22 cell numbers in a general pediatric population with filaggrin haploinsufficiency: The Generation R Study

Clinical examination for hyperlinear palms to determine filaggrin genotype: A diagnostic test accuracy study

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