Human genetics and genomics as a unifying factor for harmony and progress in Africa: a report from the 12 African Society of Human Genetics meeting in Bamako, Mali.

Since its inception in 2003, the African Society of Human Genetics (AfSHG) has been central to the promotion of genetics research on the continent, and facilitated the networking of African researchers within Africa and abroad, thereby significantly contributing to the career development of African geneticists. The continuation of these accomplishments was stimulated by the 12 international conference of AfSHG held jointly with the 1 Congress of the Malian Society of Human Genetics (MSHG) in Bamako, Mali from September 18 to 21 2019. The main theme of the conference was "Human Genetics and Genomics as a Unifying Factor for Harmony and Progress in Africa".

Cardiovascular complications in vascular connective tissue disorders after COVID-19 infection and vaccination.

Background: COVID-19 infection and vaccination have been reported to confer an elevated risk for cardiovascular events (CVE). We sought to determine whether individuals with an underlying vascular connective tissue disorder including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), or vascular Ehlers Danlos syndrome (vEDS) are at increased risk for cardiac events after COVID-19 infection or vaccination.

Methods: 325 respondents self-reported data through a cross-sectional, web-based survey available from 22 November 2021, through 15 March 2022 regarding COVID-19 illness and vaccinations, the occurrence of any CVE, and adverse events following vaccination.

Regulation of human interferon signaling by transposon exonization.

Innate immune signaling is essential for clearing pathogens and damaged cells and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I interferon receptor IFNAR2.

Role of ACSBG1 in Brain Lipid Metabolism and X-Linked Adrenoleukodystrophy Pathogenesis: Insights from a Knockout Mouse Model.

"Bubblegum" acyl-CoA synthetase (ACSBG1) is a pivotal player in lipid metabolism during mouse brain development, facilitating the activation of long-chain fatty acids (LCFA) and their incorporation into lipid species that are crucial for brain function. ACSBG1 converts LCFA into acyl-CoA derivatives, supporting vital metabolic processes. Fruit fly mutants lacking ACSBG1 exhibited neurodegeneration and had elevated levels of very long-chain fatty acids (VLCFA), characteristics of human X-linked adrenoleukodystrophy (XALD).

BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations.

An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge of manifestations and mutational spectrum is lacking. To address this, we performed detailed analysis of 42 individuals with BCL11A-related IDD (BCL11A-IDD, a.k.

Suction use in ureterorenoscopy: A systematic review and meta-analysis of comparative studies.

Objectives: Ureterorenoscopy is seeing a bloom of technological advances, one of which is incorporating suction. The objective of this study is to systematically review existing literature regarding suction use in rigid and flexible ureterorenoscopy and perform meta-analysis of studies comparing suction versus no suction ureteroscopy or mini percutaneous nephrolithotomy (PCNL).

Methods: A literature search was performed (November 2023) in MEDLINE, Embase and Cochrane CENTRAL.

Single-cell transcriptomics reveals the cellular identity of a novel progenitor population crucial for murine neural tube closure.

Neural tube closure in vertebrates is achieved through a highly dynamic and coordinated series of morphogenic events involving neuroepithelium, surface ectoderm, and neural plate border. Failure of this process in the caudal region causes spina bifida. Grainyhead-like 3 (GRHL3) is an indispensable transcription factor for neural tube closure as constitutive inactivation of the gene in mice leads to fully penetrant spina bifida.

Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells.

Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. In this study, hPSC lines from multiple donors were differentiated toward neuroectoderm and mesendoderm lineages. We revealed dynamic transcriptomic patterns that delineate the emergence of these lineages, which were conserved across lines, along with individual line-specific transcriptional signatures that were invariant throughout differentiation.

HNRNPA1 de novo Variant Associated with Early Childhood Onset, Rapidly Progressive Generalized Myopathy.

HNRNPA1 variants are known to cause degenerative motoneuron and muscle diseases which manifests in middle age or later. We report on a girl with early childhood onset, rapidly progressive generalized myopathy including ultrastructural findings in line with a proteinopathy. Proteomics of patient-derived muscle and combined screening of genomic data for copy number variations identified a HNRNPA1 de novo intragenic deletion as causative for the phenotype.

Cell type-specific expression of angiotensin receptors in the human lung with implications for health, aging, and chronic disease.

The renin-angiotensin system is a highly characterized integrative pathway in mammalian homeostasis whose clinical spectrum has been expanded to lung disorders such as chronic obstructive pulmonary disease (COPD)-emphysema, idiopathic pulmonary fibrosis (IPF), and COVID pathogenesis. Despite this widespread interest, specific localization of this receptor family in the mammalian lung is limited, partially due to the imprecision of available antibody reagents. In this study, we establish the expression pattern of the two predominant angiotensin receptors in the human lung, and , using complementary and comprehensive bulk and single-cell RNA-sequence datasets that are publicly available.

Role of ACSBG1 in brain lipid metabolism and X-linked adrenoleukodystrophy pathogenesis: Insights from a knockout mouse model.

The "bubblegum" acyl-CoA synthetase (ACSBG1) is a pivotal player in lipid metabolism during the development of the mouse brain, facilitating the activation of long-chain fatty acids (LCFAs) and their integration into essential lipid species crucial for brain function. Through its enzymatic activity, ACSBG1 converts LCFAs into acyl-CoA derivatives, supporting vital processes like membrane formation, myelination, and energy production. Its regulatory role significantly influences neuronal growth, synaptic plasticity, and overall brain development, highlighting its importance in maintaining lipid homeostasis and proper brain function.

Human Cardiac Development.

Many aspects of heart development are topographically complex and require three-dimensional (3D) reconstruction to understand the pertinent morphology. We have recently completed a comprehensive primer of human cardiac development that is based on firsthand segmentation of structures of interest in histological sections. We visualized the hearts of 12 human embryos between their first appearance at 3.

Mapping recurrent mosaic copy number variation in human neurons.

When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers.

Removing unwanted variation between samples in Hi-C experiments.

Hi-C data are commonly normalized using single sample processing methods, with focus on comparisons between regions within a given contact map. Here, we aim to compare contact maps across different samples. We demonstrate that unwanted variation, of likely technical origin, is present in Hi-C data with replicates from different individuals, and that properties of this unwanted variation change across the contact map.

An Unusual Presentation of Double-Outlet Right Atrium.

We describe an unusual example of double-outlet right atrium with separate atrioventricular junctions. The straddling and overriding tricuspid valve had two orifices, and the mitral valve was morphologically normal. An appropriate understanding of the morphology of the atrioventricular junctions, the valves, and the subvalvar apparatus, along with the location of the atrioventricular conduction axis, allowed for successful biventricular repair.

Clarifying the Anatomy of Tetralogy of Fallot with S-shaped Ascending Aorta.

We recently encountered several cases of tetralogy of Fallot with an abnormally oriented S-shaped ascending aorta. In this retrospective study, we sought to clarify morphology of this unusual under-recognized variant. Databases were reviewed to identify all patients with tetralogy of Fallot having an S-shaped ascending aorta.

Abnormal Cardiac Magnetic Resonance-Derived Ascending Aortic Area Strain Demonstrates Altered Ventriculo-Vascular Function in Marfan Syndrome.

Purpose: There remains a need for improved imaging markers for risk stratification and treatment guidance in Marfan syndrome (MFS). After aortic root replacement (ARR), vascular remodeling and progressive aneurysm formation can occur due to alterations in up- and downstream wall biomechanics and hemodynamics. We aim to compare the ventriculo-vascular properties of patients with MFS with controls, and investigate the correlation between ascending aortic area strain and descending aortic area strain (DAAS) with other clinical variables.

Follow-up of urolithiasis patients after treatment: an algorithm from the EAU Urolithiasis Panel.

Objective: To develop a follow-up algorithm for urinary stone patients after definitive treatment.

Materials And Methods: The panel performed a systematic review on follow-up of urinary stone patients after treatment (PROSPERO: CRD42020205739). Given the lack of comparative studies we critically evaluated the literature and reached a consensus on the follow-up scheme.

Web-based survey investigating cardiovascular complications in hypermobile Ehlers-Danlos syndrome after COVID-19 infection and vaccination.

Background: Hypermobile Ehlers-Danlos syndrome is a heritable connective tissue disorder associated with generalized joint hypermobility but also other multisystem comorbidities, many of which may be exacerbated during a viral illness or after a vaccination. We sought to determine whether individuals with hypermobile Ehlers Danlos syndrome report an increase in adverse events, including cardiovascular events, after COVID-19 illness or vaccination.

Methods: A cross-sectional web-based survey was made available from November 22, 2021, through March 15, 2022.