ArticleAmerican journal of human genetics2017
Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families.
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 40 citations in OpenAlex.
- Proteolytic dysregulation in the skin: insight from rare monogenic skin diseases.Cell and tissue research · 2026Review
- Functional categorization of gene regulatory variants that cause Mendelian conditions.Human genetics · 2024Review
- Iron Oxide Nanoparticles with and without Cobalt Functionalization Provoke Changes in the Transcription Profile via Epigenetic Modulation of Enhancer Activity.Nano letters · 2023Article
- Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster.Developmental cell · 2022Article
- Cathepsin B Gene Knockout Improves Behavioral Deficits and Reduces Pathology in Models of Neurologic Disorders.Pharmacological reviews · 2022Review
- A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle.PLoS genetics · 2021Article
- Chromatin Conformation in Development and Disease.Frontiers in cell and developmental biology · 2021Review
- Structural Variants Create New Topological-Associated Domains and Ectopic Retinal Enhancer-Gene Contact in Dominant Retinitis Pigmentosa.American journal of human genetics · 2020Article
- Mendelian Gene Discovery: Fast and Furious with No End in Sight.American journal of human genetics · 2019Article
- Deficiency of the human cysteine protease inhibitor cystatin M/E causes hypotrichosis and dry skin.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Beyond the Exome: The Non-coding Genome and Enhancers in Neurodevelopmental Disorders and Malformations of Cortical Development.Frontiers in cellular neuroscience · 2019Article
- Comparison of three variant callers for human whole genome sequencing.Scientific reports · 2018Article
- Enhancers: bridging the gap between gene control and human disease.Human molecular genetics · 2018Review
- Structural variation in the 3D genome.Nature reviews. Genetics · 2018Review
- Keratolytic Winter Erythema: An Update.Dermatopathology (Basel, Switzerland)Review
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Authors and funding
29 authors at 12 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis. Included in the 2.62 kb overlapping region of these duplications is an enhancer element that is active in epidermal keratinocytes. The activity of this enhancer correlated with CTSB expression in normal differentiating keratinocytes and other cell lines, but not with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and immunohistochemistry of the palmar epidermis demonstrated significantly increased expression of CTSB, as well as stronger staining of cathepsin B in the stratum granulosum of affected individuals than in that of control individuals. Analysis of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in South African and Norwegian families is caused by tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB, resulting in upregulation of this gene in affected individuals.
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