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.

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

PBMCs are essential for immunity and involved in various diseases. To identify genetic variations contributing to PBMCs transcriptome-wide gene expression, we performed a genome-wide eQTL analysis by using genome-wide SNPs data and transcriptome-wide mRNA expression data. To assess whether there are common regulation patterns shared among different tissues/organs, public datasets were utilized to identify common eQTLs shared with PBMCs in lymphoblastoid, monocytes, liver, and brain. Allelic expression imbalance (AEI) assay was employed to validate representative eQTLs identified. We identified 443 cis- and 2386 trans-eSNPs (FDR <0.05), which regulated 128 and 635 target genes, respectively. A transcriptome-wide expression regulation network was constructed, highlighting the importance of 28 pleiotropic eSNPs and 18 dually (cis- and trans-) regulated genes. Three genes, that is, TIPRL, HSPB8, and EGLN3, were commonly regulated by hundreds of eSNPs and constituted a very complex interaction network. Strikingly, the missense SNP rs371513 trans- regulated 25 target genes, which were functionally related to poly(A) RNA binding. Among 8904 eQTLs (P < 0.001) identified herein in PBMCs, a minority (163) was overlapped with lymphoblastoid, monocytes, liver, and/or brain. Besides, two cis-eSNPs in PBMC were confirmed by AEI. The present results demonstrated a comprehensive expression regulation network for human PBMCs and may provide novel insights into the pathogenesis of immunological diseases related to PBMCs.

Identification of expression quantitative trait loci (eQTLs) in human peripheral blood mononuclear cells (PBMCs) and shared with liver and brain.

To the Editor: Acne inversa (AI; OMIM: 142690) is a painful chronic follicular disease, characterized by recurrent draining sinuses and abscesses with subsequent scarring and chronic seepage, predominantly in skin folds that carry terminal hairs and apocrine glands. It mainly affects the scalp, neck, the axillae, perineum, and inframammary regions. AI significantly affects patients’ quality of life because of the chronic and recurrent nature of symptoms as well as the lack of satisfying treatment options.

Gao et al.[1] have already discovered that the genetic locus responsible for AI is located at chromosome 1p21.1-1q25.3 by genome-wide linkage scan, but could not identify any causal gene for the disease. Wang et al.[2] found independent loss-of-function mutations in presenilin enhancer gamma-secretase subunit (PSENEN), presenilin 1 (PSEN1), or Nicastrin (NCSTN), which encode essential components of the γ-secretase multiprotein complex. Liu et al.[3] further confirmed the pathogenic role of NCSTN mutations in AI by combining exome sequencing with previous genome-wide linkage analysis. Jiao et al.[4] found a novel mutation of c. 1258C >T in NCSTN, which would lead to a substitution of glutamine by a premature termination codon at amino acid 420 (p.Q420X).

In November 2014, a 33-year-old Chinese man consulted for severe facial acne associated with suppurating lesions of major body folds, which presented with typical characteristics of AI. The patient reported that cysts appeared repeatedly on his head in August 2002, subsequently, inflammatory subcutaneous nodules developed on the face, neck, and armpit [Figure 1] (the patient with AI refused to provide the photo on his face and neck, now we offer only typical photo in his armpit). Isotretinoin soft capsules, minocycline, and cephalosporins have been administered orally, while rivanol and retinoic acid cream were used on local lesions, but the lesions were not improved obviously. No other skin, nail, or hair abnormality was found. The patient denied other family member had similar lesions and denied cousins matrimony history of his parents. After physical examination by experienced clinical dermatologists, the clinical characteristics supported the diagnosis of AI.



Figure 1

Clinical features of the patient with acne inversa. Fibrosis, nodules, abscesses, and scars on the armpit.



Here, we reported this patient with AI and sequenced NCSTN, PSENEN, and PSEN1 genes. The study was approved by the Ethics Committee of Anhui Medical University and conducted according to the principles of the Declaration of Helsinki. The result of sequencing showed no causative mutation in the coding regions or splice sites of these three genes.

AI is a chronic inflammatory skin disease that presents with nodules, cysts, and abscesses in apocrine gland-bearing sites. In this study, we examined the γ-secretase genes NCSTN, PSENEN, and PSEN1 for mutations and found no mutation. This result suggests that AI is a genetically heterogeneous disorder. The causative genes of some monogenic disorders, such as disseminated superficial actinic porokeratosis,[5] have been found by linkage analysis combined with whole exome sequencing, but we did not find the mutation of these disease-causing genes in some families or sporadic patients, indicating that there may be other causative genes. Hence, additional and as yet unknown genes predispose to the development of this distressing disorder. Further study, using extensive sequencing of noncoding or regulatory sequence of these genes, is warranted.

Financial support and sponsorship
This work was supported by a grant from the National Natural Science Foundation of China (No. 81301352).


Conflicts of interest
There are no conflicts of interest.

A Case Report of Inversa Acne and Evaluation for Mutations in the NCSTN, PSENEN, and PSEN1 Genes

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A Case Report of Inversa Acne and Evaluation for Mutations in the NCSTN, PSENEN, and PSEN1 Genes