Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22

Zhong, Wanxie; Cui, Bin; Zhang, Yizhi; Jiang, Hongzhi; Wei, Shengcai; Bu, Lei; Zhao, Guoping; Hu, Landian; Kong, Xiangyin

doi:10.1007/s10038-003-0043-1

Cited by 18 publications

(8 citation statements)

References 9 publications

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“…Genetic linkage analyses on IV families mapped FLG to the epidermal differentiation complex on chromosome 1q21 12,13 . More recently, genotyping showed that loss‐of‐function mutations in the FLG gene are the cause of IV, 8 and that the condition is inherited in a semidominant manner with 83–96% penetrance 14–16 .…”

Section: Ichthyosis Vulgaris Is Defined By Mutations In Flgmentioning

confidence: 99%

Ichthyosis vulgaris: the filaggrin mutation disease

Thyssen

Godoy-Gijón

Elias

2013

British Journal of Dermatology

135

131

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Ichthyosis vulgaris is caused by loss-of-function mutations in the filaggrin gene (FLG) and is characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar hyperlinearity, and a strong association with atopic disorders. According to the published studies presented in this review article, FLG mutations are observed in approximately 7·7% of Europeans and 3·0% of Asians, but appear to be infrequent in darker-skinned populations. This clinical review article provides an overview of ichthyosis vulgaris epidemiology, related disorders and pathomechanisms. Not only does ichthyosis vulgaris possess a wide clinical spectrum, recent studies suggest that carriers of FLG mutations may have a generally altered risk of developing common diseases, even beyond atopic disorders. Mechanistic studies have shown increased penetration of allergens and chemicals in filaggrin-deficient skin, and epidemiological studies have found higher levels of hand eczema, irritant contact dermatitis, nickel sensitization and serum vitamin D levels. When relevant, individuals should be informed about an increased risk of developing dermatitis when repeatedly or continuously exposed to nickel or irritants. Moreover, with our current knowledge, individuals with ichthyosis vulgaris should be protected against neonatal exposure to cats to prevent atopic dermatitis and should abstain from smoking to prevent asthma. Finally, they should be advised against excessive exposure to factors that decrease skin barrier functions and increase the risk of atopic dermatitis.

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Section: Ichthyosis Vulgaris Is Defined By Mutations In Flgmentioning

confidence: 99%

Ichthyosis vulgaris: the filaggrin mutation disease

Thyssen

Godoy-Gijón

Elias

2013

British Journal of Dermatology

135

131

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“…The flaky tail phenotype is caused by a single autosomal recessive mutation that maps to mouse chromosome 3, 24 close to the genes encoding mouse loricrin and profilaggrin 25 . Linkage analysis in humans suggested linkage of ichthyosis vulgaris to chromosome 1q22 in two Chinese families 26 . Another study reported linkage of a clinical subtype of ichthyosis vulgaris with an absent granular epidermal layer to the chromosomal region containing the EDC 27 …”

Section: Role Of the Epidermal Differentiation Complex In The Pathogementioning

confidence: 99%

On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis

2007

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Undisturbed epidermal differentiation is crucial for an intact skin barrier function. The epidermal differentiation complex (EDC) is a cluster of genes on chromosome 1q21 encoding proteins that fulfil important functions in terminal differentiation in the human epidermis, including filaggrin, loricrin, S100 proteins and others. Recently, evidence emerged that variation within EDC genes plays an important role in the pathogenesis of three common skin disorders, ichthyosis vulgaris, atopic dermatitis (AD) and psoriasis. Two loss-of-function mutations in the filaggrin (FLG) gene, R501X and 2282del4, were identified as causative for ichthyosis vulgaris in 15 affected European families, and the mode of inheritance was found to be semidominant. As ichthyosis vulgaris and AD often occur concomitantly in affected individuals, these two mutations were subsequently investigated in AD patients and found to be strongly associated with the disease. Following this first report, seven replication studies have been performed that all confirm an association of these two mutations with AD (or AD subtypes) in several European cohorts. Additionally, two unique loss-of-function mutations in the FLG gene were identified in Japanese ichthyosis vulgaris families and found to be associated with AD in a Japanese cohort. Thus, the FLG mutations are among the most consistently replicated associations for AD. Additionally, linkage analysis has suggested that variation within the EDC might also predispose for psoriasis but the exact susceptibility variation(s) have not yet been elucidated. Taken together, these findings convincingly demonstrate the important role of barrier dysfunction in various common skin disorders.

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“…Genetic linkage analyses on IV patients mapped the FLG gene to the epidermal differentiation complex on chromosome 1q21 [ 18 ]. Loss-of-function mutations of the FLG gene have been identified to underlie IV, which is inherited in a semi-dominant model with 83–96% penetrance where heterozygotes have mild sub-clinical phenotype compared with homozygotes who with more prominent ichthyosis [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

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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Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22

Cited by 18 publications

References 9 publications

Ichthyosis vulgaris: the filaggrin mutation disease

Ichthyosis vulgaris: the filaggrin mutation disease

On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis

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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