Targeted next‐generation sequencing identifies nine novel filaggrin gene variants in Chinese Han patients with ichthyosis vulgaris

Chen, S.; Kong, Xiangdong; Wei, Xiaohua; Sun, Yan; Yin, Dan; Zhang, Q.; Du, Lei; Man, Johnny Hon-Wai; Mao, Liangwei; Li, H.; Tu, Yanhao; Yang, Yun

doi:10.1111/bjd.15588

Cited by 4 publications

(11 citation statements)

References 7 publications

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“…In recent years, efforts have been made to sequence FLG using target-region enrichment based on the next-generation sequencing (NGS) method. In 2017, a probe capture enrichment-based NGS method (Roche NimbleGen) was first used to sequence FLG in 54 Chinese Han IV patients ( 13 ). Another probe capture system-based NGS method (Agilent SureDesign, Agilent Technologies) was also developed and used for FLG sequencing in 741 children with AD ( 15 , 19 ).…”

Section: Discussionmentioning

confidence: 99%

“…Similar to other studies on FLG in AD or IV, our studies have focused only on the variants that cause pre-stop or frameshift of coding, and other types of mutations, such as missense mutations, were not included ( 13 , 15 , 16 ). This was based on the conventional opinion that truncated filaggrin proteins cannot function normally, as with the homozygous R501X, which has been shown to cause the loss of keratohyalin granules in the epidermis granular layer ( 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, in the case of FLG , Gene Ontology analysis showed that this gene was not included in any immune networks with other reported leprosy-associated genes, indicating its possible barrier role in defending against infection with Mycobacterium leprae ( 6 ). Given that a series of low-frequency and rare LoF mutations in FLG have been reported in AD and IV ( 13 – 16 ), the finding of only one leprosy-associated low-frequency (3.54%) LoF mutation (K4022X) in FLG may be not adequately convincing of the potential role of FLG in leprosy ( 6 ).…”

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confidence: 99%

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Massively Parallel Sequencingof the Filaggrin Gene Reveals an Association Between FLG Loss-of-function Mutations and Leprosy

Shi

Mi²,

Wang³

et al. 2020

Acta Derm Venereol

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Filaggrin, encoded by the FLG gene, plays a crucial role in the barrier function of epidermis, but the association between FLG loss-of-function mutations and infectious skin diseases has not been systematically studied. FLG coding sequences from 945 patients with leprosy and 916 healthy controls were captured and enriched using an array-based high-throughput system, and subjected to next-generation sequencing. The loss-of-function mutations found were further validated by Sanger sequencing. A total of 21 loss-of-function mutations were found in 945 patients with leprosy, with a carrier rate of 17.53%, while the prevalence of these mutations in 916 healthy controls was 14.77%, which was significantly lower than in patients. Two individual FLG loss-of-function mutations (K4022X and Q1790X) were found to be significantly associated with leprosy. These results suggest a possible role for filaggrin in defending against leprosy pathogens.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Massively Parallel Sequencingof the Filaggrin Gene Reveals an Association Between FLG Loss-of-function Mutations and Leprosy

Shi

Mi²,

Wang³

et al. 2020

Acta Derm Venereol

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“…Twenty-five variants in FLG were also identified in a Chinese study, 3 of which 9 (36%) were not previously reported. Targeted next-generation sequencing has identified nonsense and frame-shift variants in FLG mutations.…”

Section: What Does This Study Add?mentioning

confidence: 94%

“…Ichthyosis vulgaris is an inherited form of ichthyosis caused by loss‐of‐function mutations in the filaggrin gene (FLG) 1,2 . The clinical presentation of ichthyosis vulgaris includes xerosis, keratosis pilaris, palmar hyperlinearity and a predisposition to atopic disorders 2,3 . Ichthyosis vulgaris exhibits an autosomal semi‐dominant pattern of inheritance with a milder phenotype in heterozygotes 4,5 and an estimated prevalence of around 1:100 to 1:250 1 making it the most frequently occurring form of ichthyosis 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Ichthyosis vulgaris: An updated review

Jaffar

Shakir

Kumar

et al. 2022

Skin Health and Disease

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Ichthyosis vulgaris is an inherited, non‐syndromic form of ichthyosis that presents with skin problems. Making up more than 95% cases of ichthyosis, ichthyosis vulgaris is caused by heterozygous loss‐of‐function mutation of the filaggrin gene, raising the fragility and permeability of the stratum corneum. It typically presents in infancy as xerosis, skin lesions, keratosis pilaris, palmoplantar hyper linearity, scaly dermatosis, and erythroderma, clearly identifiable by age 5. Although majority of patients have a normal lifespan, possible complications include a vitamin D deficiency and auditory problems due to scaling in the ears, besides a drop in quality of life due to dermatological changes. Urea‐based creams with 10% urea, ceramides, and other ceramides are often the first line therapy in ichthyosis vulgaris. There is no known curative treatment for ichthyosis vulgaris, but lifelong treatment can alleviate the symptoms. Urea‐based creams are highly therapeutic, whereas ammonium lactate 12% lotion with a physiological lipid‐based repair cream can help with scaling and dryness. There is also evidence in favour of propylene glycol solutions. Risankizumab, an anti‐interleukin‐23 drug, and enhancement of natural moisturizing factors are also two highly promising solutions that require additional research. This review aims to provide updates on the manifestation, evaluation, and treatment of ichthyosis vulgaris.

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Exacerbation of ichthyosis vulgaris phenotype by co-inheritance of STS and FLG mutations in a Chinese family with ichthyosis: a case report

Wang

Shen

et al. 2018

BMC Med Genet

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BackgroundX-linked ichthyosis (XLI) is a recessive keratinization condition caused by deficient activity of steroid-sulfatase due to mutations in steroid sulfatase (STS) gene located on the X chromosome. In contrast, ichthyosis vulgaris (IV) is caused by filaggrin deficiency due to semi-dominant loss-of-function mutations of filaggrin (FLG) gene. Filaggrin defects could synergize with XLI to exacerbate its phenotype.Case presentationWe report a Chinese family with patients presenting diverse phenotype of Keratosis pilaris. A next-generation sequencing panel interrogating 25 ichthyosis related genes with sequencing coverage of the coding regions and splice site junctions, was applied to screen genetic mutations. A gross deletion encompassing the STS gene ranging from exon 1–10 and the FLG c.3321delA mutation were identified in a 31-year old male proband, one of his sister, and his mother, and all the three patients showed obvious symptom. The deletion of STS gene was confirmed by real-time quantitative PCR. The proband’s another sister and his two nephews carried only FLG c.3321delA mutation. Patients carried both mutations presented more severe symptom, while those only carried FLG c.3321delA mutation showed slight or normal phenotype.ConclusionsIn conclusion, we found that the IV phenotype was exacerbated by co-inheritance of STS and FLG mutations in a Chinese family with ichthyosis. Other genomic regions no included in the study might be also involved in phenotypic modifications.

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Targeted next‐generation sequencing identifies nine novel filaggrin gene variants in Chinese Han patients with ichthyosis vulgaris

Cited by 4 publications

References 7 publications

Massively Parallel Sequencingof the Filaggrin Gene Reveals an Association Between FLG Loss-of-function Mutations and Leprosy

Massively Parallel Sequencingof the Filaggrin Gene Reveals an Association Between FLG Loss-of-function Mutations and Leprosy

Ichthyosis vulgaris: An updated review

Exacerbation of ichthyosis vulgaris phenotype by co-inheritance of STS and FLG mutations in a Chinese family with ichthyosis: a case report

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