Mutations in the γ-secretase genes PSEN1, PSENEN, and NCSTN in a family with acne inversa

Shi, Tian-Wei; Bai, Nan; Jiang-an, Zhang; Lu, Feng; Chen, Xiaobing; Kong, Xiangdong

doi:10.1684/ejd.2018.3244

Cited by 14 publications

(10 citation statements)

References 7 publications

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“…Epidemiological studies suggest the influence of many genetic and environmental factors. In addition to family cases due to mutations in genes encoding essential components of the γ-secretase multiprotein complex (PSEN1, PSENEN, and NCSTN genes) [ 12 , 13 , 14 , 15 ], several other factors including psychological influences, metabolism, smoking habits, bacterial infections, and associations with other diseases (mainly inflammatory disorders) have been related to a higher incidence of HS [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 16 , 29 ]. Recently, our group reported on the role of several adipokines (adiponectin, leptin, resistin, and visfatin) in patients with HS and investigated the possible associations with insulin resistance, HS risk, and disease severity [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…HS has been reported in several members of different generations of various families [ 10 , 11 ]. Moreover, loss-of-function mutations in the genes encoding essential components of the γ-secretase multiprotein complex ( PSEN1 , PSENEN, and NCSTN genes) consistent with an autosomal dominant inheritance model have been reported in affected families [ 12 , 13 , 14 , 15 ]. The role of bacteria in the pathogenesis of HS is controversial.…”

Section: Introductionmentioning

confidence: 99%

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Association of Human Leukocyte Antigens Class II Variants with Susceptibility to Hidradenitis Suppurativa in a Caucasian Spanish Population

Ocejo-Vinyals

Fernández-Viña

Cantos-Mansilla

et al. 2020

JCM

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Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease of the hair follicle typically presenting recurrent, painful, and inflamed lesions on the inverse areas of the body. Although its pathogenesis remains unknown, the immune system appears to play a potential role. To date, two previous studies have not found any association between the Human Leukocyte Antigen system (HLA) and HS. In this study we analyzed the HLA-A, -B, -C; and DRB1, -DQA1, and –DQB1 allele distribution in 106 HS patients and 262 healthy controls from a Caucasian population in Cantabria (northern Spain). HLA-A*29 and B*50 were significantly more common in HS patients and A*30 and B*37 in controls, but these associations disappeared after statistical correction. DRB1*07, DQA1*02, and DQB1*02 were significantly more common in controls (p 0.026, p 0.0012, and p 0.0005, respectively) and the HLA allele DQB1*03:01 was significantly more common in HS patients (p 0.00007) after the Bonferroni correction. The DRB1*07~DQA1*02~DQB1*02 haplotype was significantly more common in controls (p < 0.0005). This is the first study showing an association between HLA-class II and HS. Our results suggest that HLA-II alleles (DRB1*07, DQA1*02, DQB1*02, and DQB1*03:01) and the DRB1*07~DQA1*02~DQB1*02 haplotype could influence resistance or susceptibility to HS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of Human Leukocyte Antigens Class II Variants with Susceptibility to Hidradenitis Suppurativa in a Caucasian Spanish Population

Ocejo-Vinyals

Fernández-Viña

Cantos-Mansilla

et al. 2020

JCM

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“…Table 2 provides a summary of known specific mutations. 6,8,9,11,[14][15][16][17][18][19][20][21][22][23][24][25] In 2011, Meng and colleagues 25 studied a family with follicular occlusion triad and identified an autosomal dominant pattern using 1p21.1-1q25.3, 6q25.1-25.2, D19S911-D19S1170 and 19q13.1-13.2 susceptibility loci; however, evaluation of 19 microsatellite markers for genotyping, linkage analysis and haplotype analysis did not identify a linkage between these sites and the family. Subsequent studies examined mutations in the c-secretase genes NCSTN, PSENEN and PSEN1, as well as the absence of mutant genes, 26 with results suggesting that hidradenitis suppurativa might be a genetically heterogeneous disease.…”

Section: Mutations In C-secretase Genes Present In Hidradenitis Suppumentioning

confidence: 99%

“…Most reports involved Chinese hidradenitis suppurativa families, with most of the mutant genes identified in NCSTN . Table provides a summary of known specific mutations …”

Section: Mutations In γ‐Secretase Genes Present In Hidradenitis Suppumentioning

confidence: 99%

A gene dysfunction module reveals the underlying pathogenesis of hidradenitis suppurativa: An update

Jiang

Huang

et al. 2019

Aust J Dermatology

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Hidradenitis suppurativa is a chronic skin disease characterised by repeated skin abscesses with sinus tracts and scar formation. Currently, the aetiology and pathogenesis of hidradenitis suppurativa remain unclear. Genetic factors, immune disorders, hormonal abnormalities, skin‐microbial dysbiosis, smoking, obesity and mechanical friction all influence hidradenitis suppurativa pathogenesis. Moreover, hidradenitis suppurativa has a familial subset with autosomal dominant transmission proposed and is related to a mutation of γ‐secretase component genes. In this review, we analyse and summarise research progress regarding the relationship between the γ‐secretase gene dysfunction and the pathogenesis of hidradenitis suppurativa.

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“…Thus, we attempted to construct a mouse model for HS according to our previous study, in which we detected a mutation in NCSTN (NCSTN c.617C>A, p.S206X) in patients with familial HS [15]. To mimic the onset on HS in human more closely, we established an animal model with a similar mutation in NCSTN and examined the changes in the components of hair follicles in these mice.…”

Section: Introductionmentioning

confidence: 99%

Effects of NCSTN Mutation on Hair Follicle Components in Mice

et al. 2022

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Background and Objectives: Hidradenitis suppurativa (HS)/acne inversa is an intractable skin disease that is characterized by destructive lesions – primarily on the flexural areas. Although its etiology is unknown, genetics is considered to be a factor of its pathology – mutations in γ-secretase genes have been identified in certain familial HS patients, and follicular occlusion is widely accepted as the primary cause of HS. But, no relationship between these mutations and the components of hair follicles has been reported. Thus, we examined changes in these components in mice with a mutation in NCSTN (a γ-secretase gene). Methods: We generated C57BL/6 mice with an NCSTN mutation and examined their expression of hair cortex cytokeratin and trichohyalin by Western blot and immunohistochemistry, in addition to nicastrin, the product of NCSTN, and NICD compared with wild-type mice. The structure of hair follicles was analyzed by hematoxylin-eosin staining and transmission electron microscopy. Results: In mice with an NCSTN mutation, HS-like skin lesions appeared after age 6 months, the pathological manifestations of which were consistent with the features of human HS. The structure of hair follicles was abnormal in mice with an NCSTN mutation versus wild-type mice, and hair cortex cytokeratin, trichohyalin, nicastrin, and NICD were downregulated in these mice. Conclusions: This NCSTN mutant mouse model could be an improved model to study early lesion development aspects of human HS pathogenesis and could perhaps be a better alternative for evaluating early-acting and preventive therapeutics for HS experimentally before clinical trials in HS patients. NCSTN mutations disrupt the development of hair follicles, leading to abnormal hair follicle structures, perhaps resulting in the onset of HS.

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Mutations in the γ-secretase genes PSEN1, PSENEN, and NCSTN in a family with acne inversa

Cited by 14 publications

References 7 publications

Association of Human Leukocyte Antigens Class II Variants with Susceptibility to Hidradenitis Suppurativa in a Caucasian Spanish Population

Association of Human Leukocyte Antigens Class II Variants with Susceptibility to Hidradenitis Suppurativa in a Caucasian Spanish Population

A gene dysfunction module reveals the underlying pathogenesis of hidradenitis suppurativa: An update

Effects of NCSTN Mutation on Hair Follicle Components in Mice

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