The rich and diverse genomics of African populations is significantly underrepresented in reference and in disease-associated databases. This renders interpreting the Next Generation Sequencing (NGS) data and reaching a diagnostic more difficult in Africa and for the African diaspora. It increases chances for false positives with variants being misclassified as pathogenic due to their novelty or rarity. We can increase African genomic data by (1) making consent for sharing aggregate frequency data an essential component of research toolkit; (2) encouraging investigators with African data to share available data through public resources such as gnomAD, AVGD, ClinVar, DECIPHER and to use MatchMaker Exchange; (3) educating African research participants on the meaning and value of sharing aggregate frequency data; and (4) increasing funding to scale-up the production of African genomic data that will be more representative of the geographical and ethno-linguistic variation on the continent. The RDWG of H3Africa is hereby calling to action because this underrepresentation accentuates the health disparities. Applying the NGS to shorten the diagnostic odyssey or to guide therapeutic options for rare diseases will fully work for Africans only when public repositories include sufficient data from African subjects.

Rapid Whole Genome Sequencing (rWGS) represents a valuable exploration in critically ill pediatric patients. Early diagnosis allows care to be adjusted. We evaluated the feasibility, turnaround time (TAT), yield, and utility of rWGS in Belgium. Twenty-one unrelated critically ill patients were recruited from the neonatal intensive care units, the pediatric intensive care unit, and the neuropediatric unit, and offered rWGS as a first tier test. Libraries were prepared in the laboratory of human genetics of the University of Liège using Illumina DNA PCR-free protocol. Sequencing was performed on a NovaSeq 6000 in trio for 19 and in duo for two probands. The TAT was calculated from the sample reception to the validation of results. Clinical utility data were provided by treating physicians. A definite diagnosis was reached in twelve (57.5%) patients in 39.80 h on average (range: 37.05–43.7). An unsuspected diagnosis was identified in seven patients. rWGS guided care adjustments in diagnosed patients, including a gene therapy, an off-label drug trial and two condition-specific treatments. We successfully implemented the fastest rWGS platform in Europe and obtained one of the highest rWGS yields. This study establishes the path for a nationwide semi-centered rWGS network in Belgium.

Background: Clinical checklists available have been developed to assess the risk of a positive Fragile X syndrome but they include relatively small sample sizes. Therefore, we carried out a meta‐analysis that included statistical pooling of study results to obtain accurate figures on the prevalence of clinical predictors of Fragile X syndrome among patients with intellectual disability, thereby helping health professionals to improve their referrals for Fragile X testing.Methods: All published studies consisting of cytogenetic and/or molecular screening for fragile X syndrome among patients with intellectual disability, were eligible for the meta‐analysis. All patients enrolled in clinical checklists trials of Fragile X syndrome were eligible for this review, with no exclusion based on ethnicity or age. Odds ratio values, with 95% confidence intervals as well as Cronbach coefficient alpha, was reported to assess the frequency of clinical characteristics in subjects with intellectual disability with and without the fragile X mutation to determine the most discriminating.Results: The following features were strongly associated with Fragile X syndrome: skin soft and velvety on the palms with redundancy of skin on the dorsum of hand [OR: 16.85 (95% CI 10.4–27.3; α:0.97)], large testes [OR: 7.14 (95% CI 5.53–9.22; α: 0.80)], large and prominent ears [OR: 18.62 (95% CI 14.38–24.1; α: 0.98)], pale blue eyes [OR: 8.97 (95% CI 4.75–16.97; α: 0.83)], family history of intellectual disability [OR: 3.43 (95% CI 2.76–4.27; α: 0.81)] as well as autistic‐like behavior [OR: 3.08 (95% CI 2.48–3.83; α: 0.77)], Flat feet [OR: 11.53 (95% CI 6.79–19.56; α:0.91)], plantar crease [OR: 3.74 (95% CI 2.67–5.24; α: 0.70)]. We noted a weaker positive association between transverse palmar crease [OR: 2.68 (95% CI 1.70–4.18; α: 0.51)], elongated face [OR: 3.69 (95% CI 2.84–4.81; α: 0.63)]; hyperextensible metacarpo‐phalangeal joints [OR: 2.68 (95% CI 2.15–3.34; α: 0.57)] and the Fragile X syndrome.Conclusion: This study has identified the highest risk features for patients with Fragile X syndrome that have been used to design a universal clinical checklist.