The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Place des génopathies mendeliennes dans les déficiences mentales sporadiques et non spécifiques

Nous avons étudié une translocation réciproque équilibrée 46,XY,t (2;5)(q32.3; p 15.2), de novo observée chez un garçon présentant une déficience mentale modérée. L'examen clinique et l'imagerie cérébrale par IRM n'ont révélé aucune anomalie. Le clonage positionnel par FISH a permis de montrer (i) qu'aucun gène n'est présent dans la région du point de cassure du chromosome 2, et (ii) que le point de cassure du chromosome 5 passe dans le deuxième intron du gène de la delta caténine CTNND2. Le gène de la delta caténine est exprimé exclusivement dans l'encéphale ; elle est notamment fortement impliquée dans la morphogenèse dentritique (1999 , Lu et al. ). Dans le syndrome du cri du chat (del 5p), il a été montré que la DM est plus sévère quand le territoire de la délétion inclut le gène de la delta caténine (2000, Medina et al.). La souris KO homozygote ctnnd2 -/- manifeste un dysfonctionnement cognitif et une altération de la plasticité synaptique hippocampique (2004, Israely et al.).TOURS-BU Médecine (372612103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation

We have identified a novel splice site mutation (IVS6-1G > A) in the disc-large homolog 3 (DLG3) gene, encoding the synapse-associated protein 102 (SAP102) in one out of 300 families with moderate to severe non-syndromic mental retardation. SAP102 is a member of the neuronal membrane-associated guanylate kinase protein subfamily comprising SAP97, postsynaptic density (PSD)95, and PSD93, which interacts with methyl-D: -aspartate receptor and associated protein complexes at the postsynaptic density of excitatory synapses. DLG3 is the first mental retardation gene directly linked to glutamate receptor signalling and trafficking, increasingly recognised as a central mechanism in the regulation of synaptic formation and plasticity in brain and cognitive development.status: publishe

Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX Consortium

Published in Human Mutation, 2007; 28 (2):207-208 at www.interscience.wiley.comThe EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers.Arjan P.M. de Brouwer, Helger G. Yntema, Tjitske Kleefstra, Dorien Lugtenberg, Astrid R. Oudakker, Bert B.A. de Vries, Hans van Bokhoven, Hilde Van Esch, Suzanne G.M. Frints, Guy Froyen, Jean-Pierre Fryns, Martine Raynaud, Marie-Pierre Moizard, Nathalie Ronce, Anissa Bensalem, Claude Moraine, Karine Poirier, Laetitia Castelnau, Yoann Saillour, Thierry Bienvenu, Chérif Beldjord, Vincent des Portes, Jamel Chelly, Gillian Turner, Tod Fullston, Jozef Gecz, Andreas W. Kuss, Andreas Tzschach, Lars Riff Jensen, Steffen Lenzner, Vera M. Kalscheuer, Hans-Hilger Ropers and Ben C.J. Hamelhttp://www.wiley.com/WileyCDA/WileyTitle/productCd-HUMU.htm