Hearing impairment (HI) is a common sensory disorder that is defined as the partial or complete inability to detect sound in one or both ears. This diverse pathology is associated with a myriad of phenotypic expressions and can be non-syndromic or syndromic. HI can be caused by various genetic, environmental, and/or unknown factors. Some ontologies capture some HI forms, phenotypes, and syndromes, but there is no comprehensive knowledge portal which includes aspects specific to the HI disease state. This hampers inter-study comparability, integration, and interoperability within and across disciplines. This work describes the HI Ontology (HIO) that was developed based on the Sickle Cell Disease Ontology (SCDO) model. This is a collaboratively developed resource built around the ‘Hearing Impairment’ concept by a group of experts in different aspects of HI and ontologies. HIO is the first comprehensive, standardized, hierarchical, and logical representation of existing HI knowledge. HIO allows researchers and clinicians alike to readily access standardized HI-related knowledge in a single location and promotes collaborations and HI information sharing, including epidemiological, socio-environmental, biomedical, genetic, and phenotypic information. Furthermore, this ontology illustrates the adaptability of the SCDO framework for use in developing a disease-specific ontology.

This study describes the roles of laboratory information management systems (LIMS) in multi-site genetics studies in Africa. We used the HiGeneS Africa project as a case study. The study participants were recruited in six African countries between 2019 to 2021. The Baobab LIMS, a server–client-based system (an African-led innovation) was used for the coordination of the biospecimen. The development phase of the LIMS showcased the team formation, data collection, biospecimen collection, and shipment strategies. The implementation phase showcased the biospecimen registration, processing, and quality control (QC) analytics. The sample QC was done using Nanodrop, Qubit, and PicoGreen/gDNATapestation assays. The results showed that a total of 3144 study participants were recruited from Cameroon, Ghana, Mali, Rwanda, Senegal, and South Africa. The biospecimen registration provided a comprehensive registry that included patient demographics, genetic information, and clinical and blood/saliva samples from the proband and family relatives. The QC analyzes identified 30 samples that failed QC, linked to overdue storage in the freezer before DNA extraction. The LIMS components implemented in this project formed a structure that can be upscaled to artificial intelligence-based LIMS. In conclusion, this study represents the largest and the most diverse collection of biospecimens for the genetic study of hearing impairment in Africa to date. A well-characterized LIMS should be recommended for multi-site molecular studies, particularly in Africa, to enhance African participation in global genomic medicine.

Fragile X Syndrome (FXS), an X-linked dominant monogenic condition, is the main genetic cause of intellectual disability (ID) and autism spectrum disorder (ASD). FXS is associated with an expansion of CGG repeat sequence in the Fragile X Mental Retardation gene 1 (FMR1) on chromosome X. Following a neuropediatric assessment of two male siblings who presented with signs of FXS that was confirmed with molecular testing, we provided cascade counselling and testing to the extended family. A total of 46 individuals were tested for FXS; among them, 58.70% (n = 27) were females. The mean age was 9.4 (±5) years for children and 45.9 (±15.9) years for adults. Pedigree analysis suggested that the founder of these families was likely a normal transmitting male. Four out of 19 males with clinical ID were confirmed to have a full mutation for FXS, while 14/27 females had a pathologic CGG expansion (>56 CGG repeats) on one of their X chromosomes. Two women with premature menopause were confirmed of being carriers of premutation (91 and 101 CGG repeats). We also identified maternal alleles (91 and 126 CGG repeats) which expanded to a full mutation in their offspring (>200 CGG repeats). This study is a rare report on FXS from Africa and illustrates the case scenario of implementing genetic medicine for a neurogenetic condition in a rural setting.