학술논문
Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts
Document Type
article
Author
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; Olawale Adamson; Chinyere Adeleke; Mary Li; Veronica Sule; Sami Kayali; Joy Olotu; Peter A. Mossey; Solomon Obiri‐Yeboah; Carmen J. Buxo; Terri Beaty; Margaret Taub; Peter Donkor; Mary L. Marazita; Oluwakemi Odukoya; Adebowale A. Adeyemo; Jeffrey C. Murray; Anya Prince; Azeez Butali
Source
Molecular Genetics & Genomic Medicine, Vol 11, Iss 10, Pp n/a-n/a (2023)
Subject
Language
English
ISSN
2324-9269
Abstract
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.