PLACK syndrome shows remarkable phenotypic homogeneity

http://bit.ly/2FGelOA

Nicastrin haploinsufficiency alters expression of type I interferon‐stimulated genes: the relationship to familial hidradenitis suppurativa

Summary

Background

Hidradenitis suppurativa (HS), also called acne inversa, is a chronic skin disease. The symptoms can be severe, and include intensely painful nodules and abscesses in apocrine‐gland rich inverse skin, such as the buttocks, under the arms and in the groin. Autosomal dominant forms of HS exist, but are rare. Some of these kindred have heterozygous loss‐of‐function rare variants in the γ‐secretase complex component nicastrin (NCSTN).

Aim

To investigate the effect of NCSTN haploinsufficiency on human keratinocytes and assess potential mechanisms for lesion development.

Methods

NCSTN was knocked down using a small hairpin RNA construct in both a keratinocyte cell line (HEK001) and an embryonic kidney cell line (HEK293), and differential gene expression was assessed using RNA microarray. Using the HEK293 line, a heterozygous deletion of NCSTN was created with CRISPR/Cas9 genome editing, and nuclear factor kappa B activity was assessed using a luciferase reporter.

Results

Compared with controls, the keratinocyte NCSTN knockdown cell line showed a significantly increased expression of genes related to the type I interferon response pathway. Both HEK001 and HEK293 knockdowns demonstrated evidence of altered growth. There was a small but significant increase in nuclear factor kappa B signalling in response to tumour necrosis factor treatment in HEK293 cells genome‐edited for reduced NCSTN.

Conclusions

Our data suggest a role for increased keratinocyte inflammatory responsiveness in familial HS. Confirming this phenotype and characterizing additional effects in different cell types will require study beyond cell lines, such as in primary cells and tissues.

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Lipoedematous scalp

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Psoriasis induced by dupilumab therapy

http://bit.ly/2FFSLd6

Acne conglobata and necrotizing scleritis: a previously unreported association

http://bit.ly/2FzJ1C0

Dermoscopy of naevi in patients with oculocutaneous albinism

Summary

Oculocutaneous albinism (OCA) increases predisposition to skin malignancies. Nevertheless, the differential diagnosis between melanoma and naevi in patients with OCA is still challenging, because pigmentary lesions have rarely been described in this population. We aimed to describe the dermoscopic patterns of naevi in patients with OCA. We prospectively evaluated 83 naevi from 37 patients with OCA in a single centre in Brazil. Lesions were analysed by eye and by dermoscopy and were grouped by dermoscopic pattern. Eight main patterns were identified: homogeneous structureless pattern (n = 28; 33.7%), globular pattern (n = 27; 32.5%), reticular pattern (n = 8; 9.6%), peripheral reticular pattern with central hypopigmentation (n = 8; 9.6%), peripheral globules (n = 8; 9.6%), irregular brown globules with pink background (n = 2; 2.4%), reticular globular disorganized pattern (n = 1; 1.2%) and peripheral reticular globular with central hypopigmentation (n = 1; 1.2%). We found previously undescribed dermoscopic patterns in patients with OCA, in addition to confirming previously described patterns. These descriptions may help the understanding of pigmented naevi in patients with OCA.

http://bit.ly/2FGRnH3

Malignant peripheral nerve sheath tumor of the transverse colon with peritoneal metastasis: a case report

Malignant peripheral nerve sheath tumors are malignant tumors arising from a peripheral nerve or displaying nerve sheath differentiation. Gastrointestinal malignant peripheral nerve sheath tumors are rare and ...

http://bit.ly/2SY5cEQ