A novel somatic mutation in GNB2 provides new insights to the pathogenesis of Sturge-Weber syndrome.

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by vascular malformations affecting skin, eyes and leptomeninges of the brain, which can lead to glaucoma, seizures and intellectual disability. The discovery of a disease-causing somatic missense mutation in the GNAQ gene, encoding an alpha chain of heterotrimeric G-proteins, has initiated efforts to understand how G-proteins contribute to SWS pathogenesis. The mutation is predominantly detected in endothelial cells and is currently believed to affect downstream MAPK signalling. In this study of six Norwegian patients with classical SWS, we aimed to identify somatic mutations through deep sequencing of DNA from skin biopsies. Surprisingly, one patient was negative for the GNAQ mutation, but instead harbored a somatic mutation in GNB2 (NM_005273.3:c.232A>G, p.Lys78Glu), which encodes a beta chain of the same G-protein complex. The positions of the mutant amino acids in the G-protein are essential for complex reassembly. Therefore, failure of reassembly and continuous signalling is a likely consequence of both mutations. Ectopic expression of mutant proteins in endothelial cells revealed that expression of either mutant reduced cellular proliferation, yet regulated MAPK signalling differently, suggesting that dysregulated MAPK signalling cannot fully explain the SWS phenotype. Instead, both mutants reduced synthesis of Yes-associated protein (YAP), a transcriptional co-activator of the Hippo signalling pathway, suggesting a key role for this pathway in the vascular pathogenesis of SWS. The discovery of the GNB2 mutation sheds novel light on the pathogenesis of SWS and suggests that future research on targets of treatment should be directed towards the YAP, rather than the MAPK, signalling pathway.

Birt-Hogg-Dubé syndrome. / Birt-Hogg-Dubé-syndrom.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant genetic disorder characterised by pulmonary cysts, fibrofolliculomas and renal tumours. The pulmonary cysts may lead to pneumothorax, and in cases of primary, spontaneous pneumothorax the syndrome should be excluded. The renal tumours are frequently malignant, but slow-growing. Screening and family assessment enable discovery of renal cancer at an early stage. The syndrome is underdiagnosed and little known.

The prevalence of skin disorders in Norwegian paediatric renal transplant recipients.

A few key publications report on the frequency of skin disorders in paediatric organ transplant recipients in Southern and Central Europe presenting cumulative incidences. We aimed to estimate frequencies of skin disorders both as cumulative incidences and prevalence data, and describe skin problems in paediatric renal transplant recipients in a Norwegian renal transplant population. Clinical examination and review of post-transplant skin diseases were conducted in 70 patients having performed renal transplantation before the age of 16 in the period 1983-2006. Viral warts were a common and persistent problem, whereas bacterial and fungal infections in the skin were few. Drug-related skin disorders were rather frequent, but usually reversible on dose reduction or change of medication. Pre-malignant and malignant skin disorders appeared only in patients > 30 years of age. Relatively high cumulative incidences and low prevalence data of most skin disorders were found in the examined patient cohort.

[Vitiligo--loss of cutaneous pigmentation]. / Vitiligo--tap av pigment i huden.

BACKGROUND: Vitiligo is an acquired pigmentary skin disorder that affects 0.5-2% of the population. Many patients contact their physician and alternative therapists for help. This review article presents an update of knowledge about vitiligo and is aimed at physicians that treat this patient group. METHOD: The article is based on literature identified on PubMed, textbooks in Dermatology and supplemented by clinical experience. RESULTS AND INTERPRETATION: Vitiligo is characterized by the absence of melanocytes in skin and hair follicles. The pathogenesis is complex with genetic, autoimmune and toxic contributors. Clinically well-defined milk-white maculae are seen in the skin, with a wide variety of spread and distribution. The debut of vitiligo is often in childhood and adolescence. Investigations indicate that vitiligo affects quality in life for both children and adults. Treatment of vitiligo is a challenge. Phototherapy with narrowband UVB or topical therapy with tacrolimus ointment or potent steroids may be indicated in some cases, but the effect is not well documented.