Wilson’s disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson’s disease ever reported of 1∶1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18±1 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson’s disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson’s disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.

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BackgroundAs a major crossroads between Asia and Europe, Romania has experienced continuous migration and invasion episodes. The precise routes may have been shaped by the topology of the territory and had diverse impacts on the genetic structure of mitochondrial DNA (mtDNA) in historical Romanian provinces. We studied 714 Romanians from all historical provinces, Wallachia, Dobrudja, Moldavia, and Transylvania, by analyzing the mtDNA control region and coding markers to encompass the complete landscape of mtDNA haplogroups.ResultsWe observed a homogenous distribution of the majority of haplogroups among the Romanian provinces and a clear association with the European populations. A principal component analysis and multidimensional scaling analysis supported the genetic similarity of the Wallachia, Moldavia, and Dobrudja groups with the Balkans, while the Transylvania population was closely related to Central European groups. These findings could be explained by the topology of the Romanian territory, where the Carpathian Arch played an important role in migration patterns. Signals of Asian maternal lineages were observed in all Romanian historical provinces, indicating gene flow along the migration routes through East Asia and Europe.ConclusionsOur current findings based on the mtDNA analysis of populations in historical provinces of Romania suggest similarity between populations in Transylvania and Central Europe, supported both by the observed clines in haplogroup frequencies for several European and Asian maternal lineages and MDS analyses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-017-0487-5) contains supplementary material, which is available to authorized users.

PTH-independent hypercalcaemia has a low prevalence in SCC patients. Hypercalcaemia is correlated with susceptibility to develop metastases in SCC. A possible mechanism is PTHrp hypersecretion by malignant keratinocytes.

Context. Suicide is a global public health issue. Bipolar disorder (BPD) has the highest suicide risk among individuals suffering from mental disorders. Serotoninergic dysfunctions have been linked to suicidal behaviour and platelet serotonin is recognised as a reliable index for the presynaptic serotonin activity.Objective. Our aim was to assess whether alterations occur in platelet serotonin concentrations in BPD type I in respect to suicide attempters compared with nonattempters.Design. This was a cross-sectional, observational study. Subjects and Methods. Plasma platelet serotonin concentrations were measured using ELISA technique in 71 BPD I patients. The participants were assigned into 3 groups (non-attempters, low lethality and high lethality suicide attempters), according to the Columbia-Suicide Severity Rating Scale. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire designed specifically for this research.Results. Our study showed significant lower levels of platelet serotonin in suicide attempters compared with non-attempters (p = 0.030) and in high-lethality attempters compared with low-lethality attempters (p = 0.015). The study recorded a higher number of total lifetime and lifetime depressive episodes for suicide attempters with BPD I.Conclusions. Our results subscribe to the importance of platelet serotonin as a reliable biomarker in suicide risk assessment.

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Non-melanoma skin cancer is one of the most common of all cancers and the incidence has increased in the last years as a result of many factors including increased tanning, life style and possible global climate change. Inflammation plays an important role in cancer development and is frequently evaluated by serum C-reactive protein (CRP) levels. PTGS2 -765C allele coding for COX-2 has been found to be associated with lower plasma levels of CRP. The objectives of this study are: evaluation of the association between PTGS2 -765G>C polymorphism and the occurrence of non-melanoma skin cancer, the relationship between this polymorphism and cyclooxygenase-2 activity in skin tissue, as well as the correlation with serum CRP levels in patients with non-melanoma skin cancer. We used PCR-RFLP technique to explore -765G>C PTGS2 gene polymorphism, colorimetric analysis for cyclooxygenase-2 activity in skin tissue and immunoturbidimetric assay for CRP serum levels in 174 patients with non-melanoma skin cancer [54 patients with basal cell carcinoma (BCC) and 120 patients with squamous cell carcinoma (SCC)] and 80 healthy subjects. PTGS2 -765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. We observed a significant increase in COX-2 activity in SCC and BCC patients compared to control tissue (0.58 ± 0.11 and 0.63 ± 0.09 U/mg protein, respectively vs. 0.16 ± 0.01 U/mg protein). BCC and SCC intra-group analysis showed lower COX-2 activity in C-allele carriers versus non-carriers (p < 0.001 and p < 0.0001, respectively). In BCC and SCC patients with GG genotype, CRP level is significantly increased compared to control group (p < 0.0001 and p < 0.0001, respectively). Intra-group comparison of CRP levels showed significantly lower CRP levels in patients carrying C-allele compared to GG homozygotes in BCC (p = 0.0001) and SCC patients (p < 0.0001). PTGS2 -765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. Regarding prognostic indicators, no consistent association emerged between PTGS2 -765G>C polymorphism and COX-2 activity or CRP levels.

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