A Novel NCSTN Gene Mutation in a Japanese Family with Hidradenitis Suppurativa.
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ABSTRACT:
SUBMITTER: Nishimori N
PROVIDER: S-EPMC9274921 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
A Novel NCSTN Gene Mutation in a Japanese Family with Hidradenitis Suppurativa.
Nishimori Nobuyuki N Hayama Koremasa K Kimura Kumiko K Fujita Hideki H Fujiwara Kyoko K Terui Tadashi T
Acta dermato-venereologica 20201006 17
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Project description:Acne inversa is a chronic inflammatory follicular disease with autosomal dominant inheritance. In recent years, many functional mutations in the NCSTN genes have been identified as the cause of familial acne inversa. Herein, we recruited four patients and seven unaffected individuals from a Chinese family and performed Sanger sequencing of the NCSTN gene. One novel frameshift mutation, c.450_459del (p.Ser 151GlnfsX48), was identified in exon 5 of the NCSTN gene. Three normal-looking children carrying the mutation were proven to be patients. We also presented a literature review from previous studies of acne inversa, suggesting that NCSTN is a hotspot gene for acne inversa. Most affected individuals experienced onset in adolescence. We confirmed the diagnosis in this family based on the mutation. This finding will help expound the relationship between the NCSTN gene and the pathogenesis of acne inversa and emphasize the value of genetic diagnosis in monogenic disorder.
| S-EPMC7992621 | biostudies-literature
Project description:BackgroundMutations in the γ-secretase enzyme subunits have been described in multiple kindreds with familial hidradenitis suppurativa (HS).ObjectiveIn this study, we report a novel nicastrin (NCSTN) mutation causing HS in a Dutch family. We sought to explore the immunobiological function of NCSTN mutations using data of the Immunological Genome Project.MethodsBlood samples of three affected and two unaffected family members were collected. Whole-genome sequencing was performed using genomic DNA isolated from peripheral blood leucocytes. Sanger sequencing was done to confirm the causative NCSTN variant and the familial segregation. The microarray data set of the Immunological Genome Project was used for thorough dissection of the expression and function of wildtype NCSTN in the immune system.ResultsIn a family consisting of 23 members, we found an autosomal dominant inheritance pattern of HS and detected a novel splice site mutation (c.1912_1915delCAGT) in the NCSTN gene resulting in a frameshift and subsequent premature stop. All affected individuals had HS lesions on non-flexural and atypical locations. Wildtype NCSTN appears to be upregulated in myeloid cells like monocytes and macrophages, and in mesenchymal cells such as fibroblastic reticular cells and fibroblasts. In addition, within the 25 highest co-expressed genes with NCSTN we identified CAPNS1, ARNT and PPARD.ConclusionThis study reports the identification a novel NCSTN gene splice site mutation which causes familial HS. The associated immunobiological functions of NCSTN and its co-expressed genes ARNT and PPARD link genetics to the most common environmental and metabolic HS risk factors which are smoking and obesity.
| S-EPMC7586943 | biostudies-literature
Project description:Hidradenitis suppurativa (HS) is a chronic debilitating disorder that can affect any areas bearing apocrine glands. Perineal HS is associated with high morbidity compared with other anatomic regions. Early-stage disease may mimic various other forms of cutaneous disorders, but as HS progresses pathognomonic skin changes occur. Clinical stage can guide the therapeutic approach, but the lowest recurrence rate is obtained by removing all involved skin and subcutaneous fat. Pruritus ani is a complex disease with a multitude of etiologies. Its management can be frustrating and disappointing for the patient and doctor alike. The key is to start with simple treatment options focusing on perianal hygiene and avoidance of the most common offending foods and beverages. If these measures fail, topical medications should be attempted before graduating to perianal injections of methylene blue as a last resort.
| S-EPMC3140336 | biostudies-other
Project description: Not available
| S-EPMC7586838 | biostudies-literature
Project description:ImportanceThe variation in both clinical appearance and responses to diverse treatment options emphasize the importance of an accurate, clinically relevant, yet easy-to-use scoring system in hidradenitis suppurativa.ObjectiveTo propose and provide validation data for the newly designed Severity Assessment of Hidradenitis Suppurativa score.Design, setting, and participantsWe prospectively assessed disease severity using Hurley staging and the modified Hidradenitis Suppurativa Score in 355 patients referred to Ruhr-University Bochum Department of Dermatology between March 2016 and June 2017. We also assessed disease severity via the Severity Assessment of Hidradenitis Suppurativa score.Main outcomes and measuresEvaluation and assessment of convergent validity and responsiveness to treatment of the Severity Assessment of Hidradenitis Suppurativa score.ResultsEighty-eight of the 355 patients (134 [37.7%] men and 221 [62.3%] women with a median [IQR] age of 40 [30-49] years) were classified as Hurley stage I, 221 were Hurley stage II, and 46 were Hurley stage III, with an overall median modified Hidradenitis Suppurativa Score of 31 (interquartile range [IQR], 19.3-53). The median total Severity Assessment of Hidradenitis Suppurativa score was 6 (IQR, 4-9), significantly different among the 3 Hurley groups. The median SAHS score for patients in Hurley stage I was 5 (IQR, 3-6), 6 (IQR, 5-9) for patients in Hurley stage II, and 9 (IQR, 7-12) for patients in Hurley stage III (P < .001, Kruskal-Wallis test). Correlation analysis showed a significant correlation between the modified Hidradenitis Suppurativa Score and the Severity Assessment of Hidradenitis Suppurativa score (r = 0.79, P < .001). Disease severity assessment before and after 3 months of conservative systemic treatment showed a significant correlation between the Severity Assessment of Hidradenitis Suppurativa score and modified Hidradenitis Suppurativa Score. Both the mHSS (P = .001) and the SAHS score (P < .001) significantly differed between the baseline visit (median mHSS, 33 [IQR, 24-52]; median SAHS score, 6 [IQR, 5-9]) and the 3-month visit (median mHSS, 28 [IQR, 15-43.5]; median SAHS score, 5 [IQR, 4-6.3]). The 2 patient-reported items demonstrated excellent test-retest reliability with intraclass correlation coefficient values greater than 0.8.Conclusions and relevanceOur validation data demonstrated that the Severity Assessment of Hidradenitis Suppurativa score is a disease severity instrument that significantly correlates with Hurley staging and the modified Hidradenitis Suppurativa Score, and is responsive enough to measure treatment outcome.
| S-EPMC5885841 | biostudies-literature
Project description: Not available
| S-EPMC6464653 | biostudies-literature
Project description:BackgroundHidradenitis suppurativa (HS) is a chronic, inflammatory skin disease with a large impact on patients' health-related quality of life. However, reliable and consistent outcome measures to assess body surface area (BSA) of HS have not been established.ObjectivesTo develop and assess the reliability and validity of a novel outcome instrument for assessment of HS BSA in a clinical trial setting.MethodsQualitative interviews and focus groups were conducted from July to August 2015 and October 2017 to January 2018. Evaluation of the measurement was assessed during a single-day grading session with patients in April 2018. Participants, who included clinicians or patients, were recruited from academic medical centres in the U.S. mid-Atlantic region.ResultsConcept elicitation included input from 10 providers, of which 60% (n = 6) were female, 80% (n = 8) dermatology specialists and 20% (n = 2) gynaecology specialists. Cognitive debriefing was conducted with 11 providers, of which 82% (n = 9) were dermatologists and 18% (n = 2) gynaecologists. The evaluation stage included 10 clinicians and 23 patients. The intraclass correlation coefficient (ICC) for inter-rater reliability was 0·60 [95% confidence interval (CI) 0·44-0·74]. The ICC for intrarater reliability was 0·98 (95% CI 0·94-1·00). Transformation of the BSA score resulted in an increase in inter-rater reliability to 0·75 (95% CI 0·62-0·85) or 0·76 (95% CI 0·62-0·85). Scores all demonstrated concurrent validity, with statistically significant correlations with extant scoring methods.ConclusionsThis novel scale is a reliable and valid HS outcome instrument and may capture a wide range of patients by assessing BSA. Future research is necessary to demonstrate its responsiveness. What's already known about this topic? The major HS disease activity scales rely on lesions counts and have moderate-to-good reliability. Body surface area (BSA) is one of the physical signs included in the Core Outcome Set for HS, but is not a part of existing HS disease activity scales. What does this study add? A novel disease severity scale, the Severity and Area Score for Hidradenitis (SASH), was developed and the psychometric properties assessed. There was high inter-rater reliability of 0·75 and 0·76 when BSA was scored on an ordinal scale, and an excellent intrarater reliability of 0·98. The SASH score also demonstrated convergent validity with extant instruments. What are the clinical implications of this work? The ability of clinicians to accurately assess disease status will be improved. Implementation of the SASH score will help guide and assess the effectiveness of appropriate treatment choice.
| S-EPMC6928447 | biostudies-literature
Project description:BackgroundHidradenitis suppurativa (HS) is a chronic auto-inflammatory skin condition characterized by nodules, abscesses, and fistulae in skin folds. The underlying pathogenesis of HS remains unclear, and effective therapeutic drugs are limited.MethodsWe acquired mRNA expression profiles from the Gene Expression Omnibus (GEO) database and conducted differential expression analysis between control and HS samples using R software. Four machine learning algorithms (SVM, RF, ANN, and lasso) and WCGNA were utilized to identify feature genes. GO, KEGG, Metascape, and GSVA were utilized for the enrichment analysis. CIBERSORT and ssGSEA were employed to analyze immune infiltration.ResultsA total of 29 DEGs were identified, with the majority showing up-regulation in HS. Enrichment analysis revealed their involvement in immune responses and cytokine activities. KEGG analysis highlighted pathways such as IL-17 signaling, rheumatoid arthritis, and TNF signaling in HS. Immune infiltration analysis revealed the predominant presence of neutrophils, monocytes, and CD8 T cells. Machine learning algorithms and WCGNA identified KYNU as a feature gene associated with HS. We have also identified 59 potential drugs for HS based on the DEGs. Additionally, ceRNA network analysis identified the MUC19_hsa-miR-382-5p_KYNU pathway as a potential regulatory pathway.ConclusionsKYNU emerged as a feature gene associated with HS, and the ceRNA network analysis identified the MUC19_hsa-miR-382-5p_KYNU pathway as a potential regulator.
| S-EPMC10668573 | biostudies-literature
Project description:ImportanceFew simplified instruments exist for use in hidradenitis suppurativa (HS) trials.ObjectiveTo assess psychometric properties of the Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA) score using a clinical trial data set.Design, setting, and participantsThis retrospective analysis of a phase 2 randomized double-blind, placebo-controlled, active-reference arm trial (UCB HS0001) included adults with moderate-to-severe HS.ExposuresTrial participants were randomized at baseline to receive bimekizumab, adalimumab, or placebo.Main outcomes and measuresThe HS-IGA score at prespecified time points up to 12 weeks after randomization.ResultsThe HS-IGA score showed strong convergent validity with IHS4 and HS-PhGA scores at baseline (Spearman correlation, 0.86 [P < .001] and 0.74 [P < .001], respectively) and at week 12 (Spearman correlation, 0.73 [P < .001] and 0.64 [P < .001], respectively). The HS-IGA scores assessed during predosing visits at screening and baseline showed good test-retest reliability (intraclass correlation coefficient [ICC] = 0.92). At week 12, HS-IGA responders were significantly associated with HiSCR-(50/75/90) responders (χ2 = 18.45; P < .001; χ2 = 18.11; P < .001; and χ2 = 20.83; P < .001, respectively). The HS-IGA score was predictive of HiSCR-50/75/90 and HS-PhGA response at week 12 (AUC, 0.69, 0.73, 0.85, and 0.71, respectively). However, the HS-IGA as a measure of disease activity showed low predictive validity with patient-reported outcomes at week 12.Conclusions and relevanceThe HS-IGA score demonstrated good psychometric properties compared with existing measures and may be considered for use as an end point in clinical trials for HS.
| S-EPMC10134037 | biostudies-literature
Project description:Hidradenitis Suppurativa is a burdensome inflammatory skin disease with significant quality of life impact. These management guidelines were developed to direct appropriate clinical management in the Australasian context. A systematic review was used for the basis of the consensus guidelines. Thirteen clinical experts were involved in a modified Delphi consensus process to develop the guidelines and treatment algorithms. Overall management strategies include appropriate severity assessment of disease and comorbidities, multimodal therapy with systemic and local treatments, and evidence-based progression along the therapeutic ladder in the event of inadequate response. Sequential monotherapy with antibiotics and/or single agent therapy is discouraged and aggressive treatment of moderate to severe disease to capture the window of opportunity is highly emphasised. Specific considerations in the setting of disease comorbidities, pregnancy and breastfeeding are also addressed. Overall, the complex nature of HS requires a complex and multimodal therapeutic response with medical, physical and surgical therapies to achieve best patient outcomes.
| S-EPMC11898165 | biostudies-literature