Denys Knight Sambrook
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PROVIDER: S-EPMC1123054 | biostudies-literature | 2002 May
REPOSITORIES: biostudies-literature
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Project description:In over 100 neuroscience genetics reports on SLC6A4 published in the first part of 2012, >40% reported data from genotyping only the serotonin transporter-linked promoter region [5HTTLPR] indel, omitting genotyping of two nearby SNPs that substantially alter 5HTTLPR allele frequencies and functionality. And 25% of these papers did not report ethnicity of the subjects genotyped, another factor that alters allele frequencies. This field thus seems stultified. Improved science for the present and future will be better served by attention to more complete methods for genotyping and subject sample reporting.
| S-EPMC3547485 | biostudies-literature
Project description:BackgroundDenys-Drash syndrome (DDS) is a rare disease caused by mutations in exons 8 and 9 of the WT1 gene. It is characterized by the association of early onset steroid-resistant nephrotic syndrome (SRNS), Wilms' tumour and, in some patients, intersex disorders, with increasing risk of gonadoblastoma. There are few published data concerning the long-term outcome of patients with DDS. The aim of this study was to report our experience.MethodsData were collected from five children (three boys) with confirmed DDS diagnosed from 1996 to 2017. The mean follow-up of these patients was 16 years.ResultsThe patients presented with SRNS and diffuse mesangial sclerosis at renal biopsy. All patients were hypertensive and progressed to end-stage kidney disease, initiating dialysis at a mean age of 28 months. Three patients developed Wilms' tumour 9 months after the SRNS was identified, which was treated by nephrectomy and chemotherapy. All five patients received kidney transplantation. SRNS did not recur after transplantation in any of the patients and graft survival was similar to that of other kidney transplant recipients in our programme. All three boys had ambiguous genitalia and cryptorchidism but a confirmed male karyotype (46, XY). One girl presented with gonadal agenesis, whereas the other one had normal female ovarian tissue and external genitalia. Both girls had a female karyotype (46, XX). Gonadoblastoma was not observed at any case.ConclusionsEarly DDS recognition in patients with SRNS is crucial due to its low prevalence, the specific treatment approach required and early detection of Wilms' tumour. Few data are available regarding long-term outcomes.
| S-EPMC6885669 | biostudies-literature
Project description:Daily, circadian rhythms influence essentially all living organisms and affect many physiological processes from sleep and nutrition to immunity. This ability to respond to environmental daily rhythms has been conserved along evolution, and it is found among species from bacteria to mammals. The hematopoietic process of the crayfish Pacifastacus leniusculus is under circadian control and is tightly regulated by astakines, a new family of cytokines sharing a prokineticin (PROK) domain. The expression of AST1 and AST2 are light-dependent, and this suggests an evolutionarily conserved function for PROK domain proteins in mediating circadian rhythms. Vertebrate PROKs are transmitters of circadian rhythms of the suprachiasmatic nucleus (SCN) in the brain of mammals, but the mechanism by which they function is unknown. Here we demonstrate that high AST2 expression is induced by melatonin in the brain. We identify RACK1 as a binding protein of AST2 and further provide evidence that a complex between AST2 and RACK1 functions as a negative-feedback regulator of the circadian clock. By DNA mobility shift assay, we showed that the AST2-RACK1 complex will interfere with the binding between BMAL1 and CLK and inhibit the E-box binding activity of the complex BMAL1-CLK. Finally, we demonstrate by gene knockdown that AST2 is necessary for melatonin-induced inhibition of the complex formation between BMAL1 and CLK during the dark period. In summary, we provide evidence that melatonin regulates AST2 expression and thereby affects the core clock of the crustacean brain. This process may be very important in all animals that have AST2 molecules, i.e. spiders, ticks, crustaceans, scorpions, several insect groups such as Hymenoptera, Hemiptera, and Blattodea, but not Diptera and Coleoptera. Our findings further reveal an ancient evolutionary role for the prokineticin superfamily protein that links melatonin to direct regulation of the core clock gene feedback loops.
| S-EPMC3605217 | biostudies-literature
Project description:ObjectiveDenys-Drash syndrome (DDS) is defined by the triad of Wilms tumor, nephrotic syndrome, and/or ambiguous genitalia. Genetic testing may help identify new gene mutation sites and play an important role in clinical decision-making.MethodsWe present a patient with an XY karyotype and female appearance, nephropathy, and Wilms tumor in the right kidney. Genomic DNA was extracted from peripheral blood cells according to standard protocols. "Next-generation" sequencing (NGS) was performed to identify novel variants. The variant was analyzed with Mutation Taster, and its function was explored by a cell growth inhibition assay.ResultsWe found the first case of Denys-Drash syndrome with the uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene. In silico analysis, the variant was predicted "disease-causing" by Mutation Taster. The mutated variant showed a weaker effect in inhibiting tumor cells than wild-type WT1.ConclusionsThe uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene may be a crucial marker in DDS.
| S-EPMC8128316 | biostudies-literature