H syndrome: A review of treatment options and a hypothesis of phenotypic variability.

H syndrome is a rare autosomal recessive disorder with clinical features comprising: hyperpigmentation, hypertrichosis, hearing loss, heart anomalies, low height, hypogonadism and hepatosplenomegaly. H syndrome results from loss-of-function mutations in SLC29A3 which leads to abnormal proliferation and function of histiocytes. Herein, we discuss the considerable phenotypic heterogeneity detected in a consanguineous Egyptian family comprising of four affected siblings, two of which are monozygotic twin and the possible therapeutics.

Phenotypic suppression of acral peeling skin syndrome in a patient with autosomal recessive congenital ichthyosis.

Autosomal recessive congenital ichthyosis (ARCI) manifests with generalized scaling often associated with generalized erythema. Mutations in at least 13 different genes have been reported to cause ARCI. Acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder manifesting with peeling over the distal limbs and dorsal surfaces of hands and feet.

Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa.

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder due to a lack of type VII collagen. At present, treatment is mainly supportive.

Objectives: To determine whether intravenous allogeneic bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) are safe in RDEB adults and if the cells improve wound healing and quality of life.

Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa.

BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) is a severe form of skin fragility disorder due to mutations in COL7A1 encoding basement membrane type VII collagen (C7), the main constituent of anchoring fibrils (AFs) in skin. We developed a self-inactivating lentiviral platform encoding a codon-optimized COL7A1 cDNA under the control of a human phosphoglycerate kinase promoter for phase I evaluation.METHODSIn this single-center, open-label phase I trial, 4 adults with RDEB each received 3 intradermal injections (~1 × 106 cells/cm2 of intact skin) of COL7A1-modified autologous fibroblasts and were followed up for 12 months.

Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02.

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis.

Serum levels of high mobility group box 1 correlate with disease severity in recessive dystrophic epidermolysis bullosa.

In the inherited blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB), there is clinical heterogeneity with variable scarring and susceptibility to malignancy. Currently, however, there are few biochemical markers of tissue inflammation or disease progression. We assessed whether the non-histone nuclear protein, high mobility group box 1 (HMGB1), which is released from necrotic cells (including keratinocytes in blister roofs), might be elevated in RDEB and whether this correlates with disease severity.

Effects of the UK Biobank collection protocol on potential biomarkers in saliva.

Background: The UK Biobank (UKB) is a national epidemiological study of the health of 500 000 people, aged 40-69 years, who completed health-related tests and a questionnaire and gave samples of blood and urine. Salivas collected from 120 000 of these subjects were transported at 4°C and were placed in ultra-low temperature archives at up to 24 h after collection. The present study assessed how changes in saliva composition under UKB conditions influence a range of potential biomarkers resulting from holding saliva at 4°C for 24 h.

Protein and mucin retention on oral mucosal surfaces in dry mouth patients.

Oral homeostasis depends largely on proteins and mucins present in saliva that coat all oral surfaces. The present study compared the protein composition of residual fluid on mucosal surfaces in subjects with normal salivary flow with that of patients with dry mouth caused by salivary hypofunction. Samples of residual mucosal fluid were collected using paper strips and then analysed by protein electrophoresis and immunoblotting.

Ras-MEK-ERK signaling cascade regulates androgen receptor element-inducible gene transcription and DNA synthesis in prostate cancer cells.

Treatment of prostate cancer (CaP) patients frequently involves androgen ablation, but resistance often develops and androgen-insensitive tumors emerge. The molecular basis for the development of refractory CaP that grows in an androgen-independent manner is poorly understood, but alterations in growth factor signaling pathways are likely to be involved. We examined the growth factor modulation of androgen-receptor element (ARE)-inducible luciferase reporter gene activity and consequent DNA synthesis as a measure of proliferative growth in androgen-dependent LNCaP or androgen-independent PC3 or DU145 CaP cells.

Selenium- or quercetin-induced retardation of DNA synthesis in primary prostate cells occurs in the presence of a concomitant reduction in androgen-receptor activity.

Prostate cancer (CaP) is the most common male malignancy in the Western world. Selenium or quercetin may down-regulate prostate-cell proliferation in immortalised cells (e.g.