RESUMO
BACKGROUND: Microcephaly with nephrotic syndrome is a rare co-occurrence, constituting the Galloway-Mowat syndrome (GAMOS), caused by mutations in WDR73 (OMIM: 616144). However, not all patients harbour demonstrable WDR73 deleterious variants, suggesting that there are other yet unidentified factors contributing to GAMOS aetiology. METHODS: Autozygosity mapping and candidate analysis was used to identify deleterious variants in consanguineous families. Analysis of patient fibroblasts was used to study splicing and alterations in cellular function. RESULTS: In two consanguineous families with five affected individuals from Turkey with a GAMOS-like presentation, we identified a shared homozygous variant leading to partial exon 4 skipping in nucleoporin, 107-KD (NUP107). The founder mutation was associated with concomitant reduction in NUP107 protein and in the obligate binding partner NUP133 protein, as well as density of nuclear pores in patient cells. CONCLUSION: Recently, NUP107 was suggested as a candidate in a family with nephrotic syndrome and developmental delay. Other NUP107-reported cases had isolated renal phenotypes. With the addition of these individuals, we implicate an allele-specific critical role for NUP107 in the regulation of brain growth and a GAMOS-like presentation.
Assuntos
Hérnia Hiatal/genética , Microcefalia/genética , Mutação/genética , Nefrose/genética , Síndrome Nefrótica/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Esteroides/metabolismo , Adolescente , Criança , Deficiências do Desenvolvimento/genética , Feminino , Homozigoto , Humanos , Lactente , Rim/metabolismo , Masculino , Linhagem , Fenótipo , Proteínas/genética , TurquiaRESUMO
OBJECTIVE: To assess the proportion of Washington state clinics that offer the copper IUD in rural vs urban settings. STUDY DESIGN: We employed a simulated patient model to survey clinics in the Human Health Resources and Services Administration 340B database to primarily assess the availability of the copper IUD. RESULTS: We successfully surveyed 194/212 (92%) clinics. More urban than rural clinics reported copper IUD availability (76/97 [78%] vs 49/97 [51%]; p < 0.01). CONCLUSIONS: Rural clinics are less likely than urban clinics to have the copper IUD available. IMPLICATIONS: The frequency of unintended pregnancies is high in the United States. We should focus our attention on decreasing barriers to the copper IUD as a long-acting reversible contraceptive, particularly for women living in rural settings.
RESUMO
The Brazilian Sucro-energy Sector produces both energy, in the form of ethanol fuel, industrial steam and electricity, and sugar. Centro de Tecnologia Canavieira (CTC), the leading Brazilian sugarcane breeding company, has developed a pipeline of insect-protected sugarcane varieties to control sugarcane borer damage. The goal of this manuscript is to present the results of studies with three genetically modified (GM) sugarcane varieties and to evaluate the published literature regarding the possible presence of GM sugarcane DNA or protein in raw or refined sugar. Specifically, two varieties of approved GM sugarcane, CTC91087-6 and CTC175-A, and an experimental CTC variety, were grown in four individual plots to produce four batches each of processed raw sugar using standard smaller-scale laboratory processing methods resulting in a total of 12 independent batches of raw sugar. Herein, we report the development of event-specific probes and DNA detection methods, designed to detect the junction of sugarcane genomic DNA and the inserted DNA of the two approved GM varieties. An identical approach was used for the testing of sugar made from the experimental CTC variety. The methodology used TaqMan® real-time PCR and ELISA assays validated for the four GM proteins expressed by these three events (Cry1Ab, Cry1Ac, NPTII, and PAT (bar)). The developed assays had very low limits of detection (LODs) for the various event-specific DNA probes (7.2-25 ng/g sugar) and insecticidal and selectable marker proteins (2.9-10.9 ng/g sugar). No event-specific DNA and no GM proteins were detectable in the 12 independent batches of raw sugar produced from these three GM sugarcane events. The results of this study, using very sensitive methods and testing several sugar batches, extend the conclusions of previous studies, reviewed herein, that showed the extensive degradation and removal of DNA and protein during sugarcane processing. Overall, these results indicate that there are no distinguishable differences between the highly purified, chemically defined sugar produced from conventional or GM varieties.