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Clinically actionable secondary findings in 130 triads from sub-Saharan African families with non-syndromic orofacial clefts
Journal article   Open access   Peer reviewed

Clinically actionable secondary findings in 130 triads from sub-Saharan African families with non-syndromic orofacial clefts

Abimbola Oladayo, Lord Jephthah Joojo Gowans, Waheed Awotoye, Azeez Alade, Tamara Busch, Thirona Naicker, Mekonen A Eshete, Wasiu L Adeyemo, Jacqueline B Hetmanski, Erliang Zeng, …
Molecular genetics & genomic medicine, Vol.11(10), e2237
10/2023
DOI: 10.1002/mgg3.2237
PMCID: PMC10568375
PMID: 37496383
url
https://doi.org/10.1002/mgg3.2237View
Published (Version of record) Open Access

Abstract

INTRODUCTION The frequency and implications of secondary findings (SFs) from genomic testing data have been extensively researched. However, little is known about the frequency or reporting of SFs in Africans, who are underrepresented in large-scale population genomic studies. The availability of data from the first whole-genome sequencing for orofacial clefts in an African population motivated this investigation. METHODS In total, 130 case-parent trios were analyzed for SFs within the ACMG SFv.3.0 list genes. Additionally, we filtered for four more genes (HBB, HSD32B, G6PD and ACADM). RESULTS We identified 246 unique variants in 55 genes; five variants in four genes were classified as pathogenic or likely pathogenic (P/LP). The P/LP variants were seen in 2.3% (9/390) of the subjects, a frequency higher than ~1% reported for diverse ethnicities. On the ACMG list, pathogenic variants were observed in PRKAG (p. Glu183Lys). Variants in the PALB2 (p. Glu159Ter), RYR1 (p. Arg2163Leu) and LDLR (p. Asn564Ser) genes were predicted to be LP. CONCLUSION This study provides information on the frequency and pathogenicity of SFs in an African cohort. Early risk detection will help reduce disease burden and contribute to efforts to increase knowledge of the distribution and impact of actionable genomic variants in diverse populations.
Sub-Saharan Africa ACMG guideline orofacial clefts secondary findings whole genome sequencing UIOWA OA Agreement

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