Fanconi anaemia in black South African patients heterozygous for the FANCG c.637-643delTACCGCC founder mutation

Background. Fanconi anaemia (FA) is an autosomal recessive, genetically heterogeneous disorder, characterised by interstrand crosslink-induced chromosome breaks, congenital abnormalities and predisposition to malignancies. It has a prevalence of about 1/40 000 in black South Africans (SAs). A founder mutation in the FANCG gene occurs in the homozygous state in 77.5% of southern African blacks. Objective. To locate additional pathogenic mutations in the FANCG gene of black FA patients who were heterozygous for the founder mutation. Methods. Further mutation analysis of the FANCG gene was undertaken in 7 patients clinically suspected of having FA. The parents of two of the patients were tested for the presence of the founder mutation to determine true heterozygosity in the patients. To clarify whether or not previously unreported variants were pathogenic, 58 random black SA individuals were screened. Results. Three novel single base pair deletions, resulting in frameshift mutations (c.247delA, c.179delT and c.899delT) were identified in 3/7 patients. A fourth patient was found to have a single base substitution resulting in a splice site mutation (c.1636+1G>A). The remaining three patients were not found to harbour any pathogenic mutations. Two non-pathogenic variants were also identified among the seven patients. Conclusion. The results of this small sample suggest that a second common mutation in the FANCG gene is unlikely in this population. However, FANCG sequencing should be performed on patients heterozygous for the common founder mutation to attempt to confirm their diagnosis.

Possible futures for rural East Africa under a changing climate: HyCRISTAL climate narrative rural infographic and Brief

The stories on the infographic and detailed in the accompanying brief describe three possible futures for rural East Africa in 2050. How the climate will change in the coming decades is uncertain, so three different plausible futures are included to demonstrate this range. These futures do not cover every possible outcome projected by climate models. The stories also describe some of the resulting impacts that could be experienced in rural areas. However, these impacts will vary across the region due to a range of local factors

Scientific understanding of East African climate change from the HyCRISTAL project

Integrating Hydro-Climate Science into Policy Decisions for Climate-Resilient Infrastructure and Livelihoods in East Africa (HyCRISTAL) is a Future Climate for Africa (FCFA) project funded to deliver new understanding of East African climate change and its impacts, and to demonstrate use of climate change information in long-term decision-making in the region. Here, we briefly summarise key findings from HyCRISTAL so far on climate change, as well as key findings from the pan-African FCFA project “IMPALA” relevant to East Africa, both in the context of previous literature on the topic

Scientific understanding of East African climate change from the HyCRISTAL project

Integrating Hydro-Climate Science into Policy Decisions for Climate-Resilient Infrastructure and Livelihoods in East Africa (HyCRISTAL) is a Future Climate for Africa (FCFA) project funded to deliver new understanding of East African climate change and its impacts, and to demonstrate use of climate change information in long-term decision-making in the region. Here, we briefly summarise key findings from HyCRISTAL so far on climate change, as well as key findings from the pan-African FCFA project “IMPALA” relevant to East Africa, both in the context of previous literature on the topic

Effectiveness of Chest Physiotherapy in Infants Hospitalized with Acute Bronchiolitis: A Multicenter, Randomized, Controlled Trial

Vincent Gajdos and colleagues report results of a randomized trial conducted among hospitalized infants with bronchiolitis. They show that a physiotherapy technique (increased exhalation and assisted cough) commonly used in France does not reduce time to recovery in this population

Micronucleus assay for Fanconi Anaemia diagnosis with ionising radiation and mitomycin C

Introduction: Fanconi Anaemia (FA) is a cancer - prone chromosomal instability disorder characterized by congenital and developmental abnormalities, bone marrow failure, defects in DNA repair and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC). Twenty different genetic subtypes of FA have been described and are associated with DNA repair pathways. Mutations in DNA repair genes could be reflected in chromosomal radiosensitivity. Clinical radiosensitivity in FA patients has previously been described. This study aimed to evaluate the in vitro chromosomal radiosensitivity and genomic instability of 14 FA patients and their parents by comparing it to healthy controls using 3 different micronucleus (MN) assays. Materials and Methods: In the cytokinesis block G0 MN assay, heparinised blood in culture medium was irradiated to 2 and 4Gy ionising radiation and immediately stimulated with phytohaemagglutinin (PHA). Cytochalasin B (Cyto B) blocked cytokinesis 23 hours after stimulation. Seventy hours post irradiation, cells were harvested. In the S/G2 MN assay, the cultures were first stimulated with PHA. The cultures were then irradiated 72 hours after stimulation with similar doses as in the G0 MN assay. Cytokinesis was immediately blocked by addition of Cyto B after irradiation. Cells were harvested 8 hours post irradiation. The MMC MN assay was conducted in similar manner as the G0 MN assay; however, the cell damage was induced by the addition of MMC. Slides were stained with acridine orange. Micronuclei were scored using a fluorescent microscope. Results: FA patients demonstrated significantly higher spontaneous and radiation-induced MN frequencies when compared to parents and healthy controls in both the G0 and S/G2 phase. FA patients also exhibited higher MMC-induced chromosomal aberrations. Conclusions: FA patients present with higher chromosomal radiosensitivity and genomic instability when compared to healthy controls. The MMC MN assay is the most sensitive assay to demonstrate differences between FA patients, parents and control

Chromosomal radiosensitivity and genomic instability of Fanconi Anemia Patients in South Africa

Introduction: Fanconi Anaemia (FA) is an autosomal recessive disorder characterized by defects in DNA repair associated with chromosomal instability and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC). The clinical manifestation includes congenital and developmental abnormalities and bone marrow failure. FA is also cancer-prone with increased incidence of cancer. Fifteen different genetic subtypes of FA have been described. In South Africa, with mixed ethnicity in the population, prevalence of FA ranges between is 1/22 000 for the white Afrikaners to 1/40 000 in the black South Africans. Evidence suggests that FA patients are chromosomally radiosensitive to ionising radiation but with very limited data. The aim of this study is to investigate chromosomal radiosensitivity and genomic instability of homozygous and heterozygous carriers of FA mutations compared to healthy individuals using the micronucleus (MN) assay. Materials and Methods: For the G0 MN assay heparinised blood in culture medium was irradiated at 0Gy (Baseline), 2Gy and 4Gy followed by the immediate stimulation of lymphocytes using phytohaemagglutinin (PHA). Cytochalasin B was added 23 hours later to inhibit cytoplasmic division. Cells were harvested 70 hours later. For the S/G2 MN assay we used the same radiation doses but the culture was only irradiated 72 hours after addition of PHA. To detect DNA damage in the S/G2 phase of the cell cycle, the cells were harvested 8 hours post irradiation. In a third assay, similar as the G0 MN assay but the cell damage is induced using MMC.All slides were stained with acridine orange and micronuclei were scored using a fluorescent microscope. Results: The micronuclei frequencies are higher in the homozygous carriers compared to the heterozygous carriers and healthy individuals. Conclusions: FA mutation carriers show higher chromosomal radiosensitivity and genomic instability compared to healthy individuals

Neodymium Nucleosynthetic Anomalies in Chondrites, the End of the Story?

info:eu-repo/semantics/publishe