New Mutations Associated with Rasopathies in a Central European Population and Genotype–Phenotype Correlations

We performed the genetic analysis of Rasopathy syndromes in patients from Central European by direct sequencing followed by next generation sequencing of genes associated with Rasopathies. All 51 patients harboured the typical features of Rasopathy syndromes. Thirty‐five mutations were identified in the examined patients (22 in PTPN11, two in SOS1, one in RIT1, one in SHOC2, two in HRAS, three in BRAF, two in MAP2K1 and two in the NF1 gene). Two of them (p.Gly392Glu in the BRAF gene and p.Gln164Lys in the MAP2K1 gene) were novel with a potentially pathogenic effect on the structure of these proteins. Statistically significant differences in the presence of pulmonary stenosis (63.64% vs. 23.81%, P = 0.013897) and cryptorchidism (76.47% vs. 30%, P = 0.040224) were identified as the result of comparison of the prevalence of phenotypic features in patients with the phenotype of Noonan syndrome and mutation in the PTPN11 gene, with the prevalence of the same features in patients without PTPN11 mutation. Cryptorchidism as a statistically significant feature in our patients with PTPN11 mutation was not reported as significant in other European countries (Germany, Italy and Greece). The majority of mutations were clustered in exons 3 (45.45%), 8 (22.73%), and 13 (22.73%) of the PTPN11 gene.     

Chikungunya Fever Outbreak,Bhutan, 2012

In 2012, chikungunya virus (CHIKV) was reported for the first time in Bhutan. IgM ELISA results were positive for 36/210 patient samples; PCR was positive for 32/81. Phylogenetic analyses confirmed that Bhutan CHIKV belongs to the East/Central/South African genotype. Appropriate responses to future outbreaks require a system of surveillance and improved laboratory capacity.     

Early outcome in renal transplantation from large donors to small and size-matched recipients - a porcine experimental model

Kidney transplantation from a large donor to a small recipient, as in pediatric transplantation, is associated with an increased risk of thrombosis and DGF. We established a porcine model for renal transplantation from an adult donor to a small or size-matched recipient with a high risk of DGF and studied GFR, RPP using MRI, and markers of kidney injury within 10 h after transplantation. After induction of BD, kidneys were removed from ～63-kg donors and kept in cold storage for ～22 h until transplanted into small (～15 kg, n = 8) or size-matched (n = 8) recipients. A reduction in GFR was observed in small recipients within 60 min after reperfusion. Interestingly, this was associated with a significant reduction in medullary RPP, while there was no significant change in the size-matched recipients. No difference was observed in urinary NGAL excretion between the groups. A significant higher level of HO-1 mRNA was observed in small recipients than in donors and size-matched recipients indicating cortical injury. Improvement in early graft perfusion may be a goal to improve short- and long-term GFR and avoid graft thrombosis in pediatric recipients.     

西藏居民卫生服务可及性影响因素及对策研究

文章借助第四次国家卫生服务调查数据,分析影响西藏居民卫生服务可及性的因素,进而提出相应建议。     

Geographical distribution of the incidence of gastric cancer in Bhutan

AIM: To estimate the prevalence of gastric cancer(GC) in a cohort of patients diagnosed with GC and to compare it with patients diagnosed with all other types of gastro-intestinal(GI) cancer during the same period.METHODS: Between 2008 and 2013,five-year period,the medical records of all GI cancer patients who underwent medical care and confirm diagnosis of cancer were reviewed at the National Referral Hospital,Thimphu which is the only hospital in the country where surgical and cancer diagnosis can be made. Demographic information,type of cancer,and the year of diagnosis were collected.RESULTS: There were a total of 767 GI related cancer records reviewed during the study period of which 354(46%) patients were diagnosed with GC. There were 413 patients with other GI cancer including; esophagus,colon,liver,rectum,pancreas,gall bladder,cholangiocarcinoma and other GI tract cancers. The GC incidence rate is approximately 0.9/10000 per year(367 cases/5years per 800000 people). The geographic distribution of GC was the lowest in the south region of Bhutan 0.3/10000 per year compared to the central region 1.4/10000 per year,Eastern region 1.2/10000 per year,and the Western region 1.1/10000 per year. Moreover,GC in the South part was significantly lower than the other GI cancer in the same region(8% vs 15%; OR = 1.8,95%CI: 1.3-3.1,P = 0.05). Among GC patients,38% were under the age of 60 years,mean age at diagnosis was 62.3(± 12.1) years with male-to-female ratio 1:0.5. The mean age among patients with all other type GI cancer was 60 years(± 13.2) and male-tofemale ratio of 1:0.7. At time of diagnosis of GC,342(93%) were at stage 3 and 4 of and by the year 2013; 80(23%) GC patients died compared to 31% death among patients with the all other GI cancer(P = 0.08).CONCLUSION: The incidence rate of GC in Bhutan is twice as high in the United States but is likely an underestimate rate because of unreported and undiagnosed cases in the villages. The high incidence of GC in Bhutan could be attributed to the high prevalence of Helicobacter pylori infection that we previously reported. The lowest incidence of GC in Southern part of the country could be due to the difference in the ethnicity as most of its population is of Indian and Nepal origin. Our current study emphasizes on the importance for developing surveillance and prevention strategies for GC in Bhutan.     

Detection of a de novo duplication of 1q32-qter by fluorescence in situ hybridisation in a boy with multiple malformations: further delineation of the trisomy 1q syndrome.

We report a dysmorphic boy with a de novo partial trisomy 1q. The boy has microcephaly, bilateral cleft lip and palate, low set and dysmorphic ears, brain anomalies, pulmonary stenosis, duodenal obstruction, dysplastic kidneys, and bifid thumbs. The trisomic segment 1q32-qter is duplicated with an inverted insertion at 1p36.3. The aberration was initially detected at amniocentesis and confirmed and defined by GTG banding, chromosome microdissection, and FISH on postnatal blood samples. The parents had normal karyotypes. De novo partial duplications of chromosome 1q have rarely been reported. Comparison of our patient with other published pure trisomy 1q cases showed similarities which allowed the further delineation of the trisomy 1q syndrome.     

Bone marrow lymphocyte subsets in myelodysplastic syndromes.

AIM--To examine lymphocyte subsets in patients with myelodysplastic syndromes (MDS); and to correlate immunohistological variables with prognosis. METHODS--Bone marrow trephine biopsy specimens from 65 patients with MDS were immunophenotyped using a panel of antibodies. A minimum of 1000 cells from representative areas of marrow sections were counted at light microscopy. The association between immunohistological variables and prognosis was assessed. RESULTS--Compared with normal control marrows (n = 23) no major abnormalities of T cells (CD3), T cell subsets (CD4, CD8, CD25, TCR gamma/delta) or natural killer cells (CD56, CD57) were seen in the 65 patients. In high risk MDS (RAEB, RAEB-t) 19% of the cases showed increased numbers of B lymphocytes compared with none in the low risk group (RA, RARS) (p < 0.0090). Only percentages of B cells above 3% significantly correlated with poor survival (p = 0.0121 for CD19, p = 0.046 for CD22). CONCLUSIONS--The deviations in T lymphocyte counts seen in peripheral blood and in bone marrow aspirates could not be verified in bone marrow biopsy specimens.