Application of Genomic Medicine in Africa: 14th Conference of the African Society of Human Genetics and the 2nd International Congress of the Moroccan Society of Genomics and Human Genetics, Rabat, Morocco 2022.

The 14th African Society of Human Genetics (AfSHG) Morocco Meeting and 2nd International Congress of the Moroccan Society of Genomics and Human Genetics (SM2GH), held in Rabat, Morocco, from December 12 through 17, 2022, brought together 298 attendees from 23 countries, organized by the AfSHG in collaboration with the SM2GH. The conference's overarching theme was "Applications of Genomics Medicine in Africa," covering a wide range of topics, including population genetics, genetics of infectious diseases, hereditary disorders, cancer genetics, and translational genetics. The conference aimed to address the lag in the field of genetics in Africa and highlight the potential for genetic research and personalized medicine on the continent. The goal was to improve the health of African populations and global communities while nurturing the careers of young African scientists in the field. Distinguished scientists from around the world shared their recent findings in genetics, immunogenetics, genomics, genome editing, immunotherapy, and ethics genomics. Precongress activities included a 2-day bioinformatics workshop, "NGS Analysis for Monogenic Disease in African Populations," and a Young Investigators Forum, providing opportunities for young African researchers to showcase their work. The vast genetic diversity of the African continent poses a significant challenge in investigating and characterizing public health issues at the genetic and functional levels. Training, research, and the development of expertise in genetics, immunology, genomics, and bioinformatics are vital for addressing these challenges and advancing genetics in Africa. The AfSHG is committed to leading efforts to enhance genetic research, coordinate training, and foster research collaborations on the continent.

Advancing genetic testing for neurological disorders in Tanzania: importance, challenges, and strategies for implementation.

This manuscript discusses the critical need for advancing genetic testing capabilities for neurological disorders (NDs) in Tanzania, emphasizing the importance, challenges, and strategies for implementation. Neurological disorders, often caused by a complex interplay of genetic and environmental factors, disproportionately affect low and middle-income countries like Tanzania. Patients with neurogenetic diagnoses in Tanzania face substantial obstacles, including lack of trust in medical professionals, stigmatization, and limited access to proper care. The manuscript underscores the infancy of genetic testing implementation for NDs in Tanzania, citing challenges such as high costs, limited availability, and the absence of routine testing in diagnostic procedures. The paper recommends establishing well-characterized cohorts, conducting a nationwide emergency census survey, and enhancing diagnostic services and healthcare financing. The paper stresses on the importance of collaboration, research, public awareness, and advocacy to address the challenges posed by NDs in Tanzania. The manuscript proposes a comprehensive plan, including training and capacity building in molecular diagnosis and bioinformatics, to establish genetic testing capabilities and reduce the burden of NDs in the country. Overall, the manuscript calls for a collaborative effort involving government support, stakeholder engagement, and international partnerships to advance genetic testing and improve healthcare outcomes for individuals with neurological disorders in Tanzania.

Implementation of a gene therapy education initiative by the ASGCT and Muhimbili University of Health and Allied Sciences.

There has been rapid growth in gene therapy development with an expanding list of approved clinical products. Several therapies are particularly relevant to patients in low- and middle-income countries. Moreover, investing in research and manufacturing presents an opportunity for economic development. To increase awareness of gene therapy, the American Society of Gene and Cell Therapy partnered with the Muhimbili University of Health and Allied Sciences, Tanzania, to create a certificate-bearing course. The goal was to provide faculty teaching in graduate and medical schools with the tools needed to add gene therapy to the university curriculum. The first virtual course was held in October of 2022, and 45 individuals from 9 countries in Africa completed the training. The content was new to approximately two-thirds of participants, with the remaining third indicating that the course increased their knowledge base. The program was well received and will be adapted for other under-resourced regions.

Novel likely pathogenic variant in NR5A1 gene in a Tanzanian child with 46,XY differences of sex development, inherited from the mosaic father.

Summary: Pathogenic variants in the nuclear receptor subfamily 5 group A member 1 gene (NR5A1), which encodes steroidogenic factor 1 (SF1), result in 46,XY and 46,XX differences of sex development (DSD). In 46,XY individuals with a pathogenic variant in the NR5A1 gene a variable phenotype ranging from mild to severe is seen, including adrenal failure, testis dysgenesis, androgen synthesis defects, hypospadias and anorchia with microphallus and infertility. We report the clinical, endocrinological and genetic characteristics of a patient with 46,XY DSD with a novel likely pathogenic missense variant in the NR5A1 gene. A retrospective evaluation of the medical history, physical examination, limited endocrinological laboratory analysis and genetic analysis with DSD gene panel testing was performed. A 1.5-month-old individual was referred with ambiguous genitalia. The karyotype was 46,XY. The endocrinological analyses were within normal male reference including a normal response of cortisol within an adrenocorticotropic hormone test. A novel heterozygous missense variant c.206G>C p.(Arg69Pro) in the NR5A1 gene was detected. This variant was present in mosaic form (~20%) in his unaffected father. Because another missense variant at the same position and other missense variants involving the same highly conserved codon have been reported, we consider this NR5A1 variant in this 46,XY DSD patient as likely pathogenic in accordance with the ACMG/AMP 2015 guidelines causing ambiguous genitalia but no adrenal insufficiency. This variant was inherited from the apparently unaffected mosaic father, which might have implications for the recurrence risk in this family. Learning points: The importance of performing trio (patient and parents) sequencing is crucial in pointing out the origin of inheritance. In a 46,XY differences of sex development patient, a normal adrenal function does not rule out an NR5A1 mutation. With the support of a dedicated overseas institute partnership, we could solve this complex clinical case by molecular diagnosis in a resource-limited setting.

Rare diseases in Tanzania: a National Call for Action to address policy and urgent needs of individuals with rare diseases.

A rare disease is generally defined as a condition which affects about 1 among 2000 people and currently, there are approximately 5000-8000 rare diseases (RDs) affecting over 400 million people world-wide. Although RDs may arise from different causes such as infections and environmental factors, about 80% are caused by genetic abnormalities. In Tanzania, there are no reports of the types of RDs, their incidence, distribution and numbers of individuals affected. In addition, there have been no strategies to map RDs in the country and develop a definition that fits the local context. Public awareness and understanding of RDs are very limited, and these lead to poor management and stigmatisation of patients. To address the ongoing problems, Tanzania joined other countries world-wide and global partners to commemorate the rare diseases day (RDD) for the first time in 2016 and subsequently every year. Unlike previous years where the RDD was organised by Ali Kimara Rare Diseases Foundation (AKRDF) with few partners, in 2020, a bigger event was co-hosted by Ali AKRDF and Tanzania Human Genetics Organization together with government representatives and other multiple partners. The organisers, government representatives and participants proposed a national "Call for Action" with the overall goal of improving the lives of patients/individuals with RDs. The call focuses and aims to address 17 strategic issues that are broadly categorised into four areas. These include generating demographic data of individuals with RDs; advocating for policies and guidelines for diagnosis, care, treatment and health financing; developing policies supporting public education, awareness and advocacy; and strengthening research, innovation and public-private partnerships. If adopted and implemented, the potential impacts of these recommendations will include improved access to adequate and high-quality health and education services, and policies and guidelines to address the current and future challenges facing individuals with RDs and their families.

"Black Lives Matter and Black Research Matters": the African Society of Human Genetics' call to halt racism in science.

The African Society of Human Genetics (AfSHG) was formed to provide a forum for human genetics and genomics scientists in Africa to interact, network, and collaborate. This is critical to facilitate development of solutions to the public health burden of many rare and common diseases across the continent. AfSHG fully supports the Black Lives Matter movement, which is dedicated to fighting racism and ensuring that society values the lives and humanity of Black people. The AfSHG would like to add its "voice" to the public outcry against racism sparked by George Floyd's death and to declare its commitment to ensuring that injustice and systematic racism, as well as abuse and exploitation of Africans and their biological material, are no longer tolerated. This is particularly relevant now as African genomic variation is poised to make significant contributions across several disciplines including ancestry, personalized medicine, and novel drug discovery. "Black Lives Matter and Black Research Matters" is AfSHG's call for the global community to support halting, and reversing, the perpetuation of exploitation of African people through neocolonial malpractices in genomic research. We also propose five key ways to curb racism in science, so that we can move forward together, with a common humanity, collectively embracing scientific endeavors.

Clinical-demographic markers for improving diabetes mellitus diagnosis in people with tuberculosis in Tanzania.

BACKGROUND: Tuberculosis (TB) control is threatened by an increasing prevalence of diabetes mellitus (DM), particularly in endemic countries. Screening for DM is not routinely implemented in Tanzania; therefore, we aimed to screen for DM at TB diagnosis using clinical-demographic markers. METHODS: Our cross-sectional study recruited TB patients who received anti-TB treatment between October 2019 and September 2020 at health care facilities in three regions from Tanzania. Patients were screened for DM using DM symptoms (polydipsia, polyphagia and polyuria) and random blood glucose (RBG) testing. Patients with a history of DM and those with no history of DM but an RBG ≥ 7.8 mmol/L had point-of-care glycated haemoglobin (HbA1c) testing, and were considered to have DM if HbA1c was ≥ 48 mmol/mol. RESULTS: Of 1344 TB patients, the mean age was 41.0 (± 17.0) years, and 64.7% were male. A total of 1011 (75.2%) had pulmonary TB, and 133 (10.4%) had at least one DM symptom. Overall, the prevalence of DM was 7.8%, of which 36 (2.8%) TB patients with no history of DM were newly diagnosed with DM by RBG testing. TB/DM patients were older than those with only TB (50.0 ± 14.0 years vs 40.0 ± 17.0 years, p < 0.001). Patients with RBG ≥ 7.8 mmol/L were more likely to have pulmonary TB (p = 0.003), age ≥ 35 years (p = 0.018), and have at least one DM symptom (p < 0.001). There was a substantial agreement (Kappa = 0.74) between the on-site glucometer and point-of-care HbA1c tests in detecting DM range of hyperglycemia. CONCLUSION: The implementation of clinical-demographic markers and blood glucose screening identified the overall prevalence of DM and those at risk of DM in TB patients. Clinical-demographic markers are independent predictors for DM range hyperglycemia and highlight the importance of further diagnostic testing and early co-management of TB and DM.

Inauguration of the Tanzania Society of Human Genetics: Biomedical Research in Tanzania with Emphasis on Human Genetics and Genomics.

Human genetics research and applications are rapidly growing areas in health innovations and services. African populations are reported to be highly diverse and carry the greatest number of variants per genome. Exploring these variants is key to realize the genomic medicine initiative. However, African populations are grossly underrepresented in various genomic databases, which has alerted scientists to address this issue with urgency. In Tanzania, human genetics research and services are conducted in different institutions on both communicable and noncommunicable diseases. However, there is poor coordination of the research activities, often leading to limited application of the research findings and poor utilization of available resources. In addition, contributions from Tanzanian human genetics research and services are not fully communicated to the government, national, and international communities. To address this scientific gap, the Tanzania Society of Human Genetics (TSHG) has been formed to bring together all stakeholders of human genetics activities in Tanzania and to formally bring Tanzania as a member to the African Society of Human Genetics. This article describes the inauguration event of the TSHG, which took place in November 2019. It provides a justification for its establishment and discusses presentations from invited speakers who took part in the inauguration of the TSHG.