TY - JOUR
T1 - Clinically actionable secondary findings in 130 triads from sub-Saharan African families with non-syndromic orofacial clefts
AU - Oladayo, Abimbola
AU - Gowans, Lord Jephthah Joojo
AU - Awotoye, Waheed
AU - Alade, Azeez
AU - Busch, Tamara
AU - Naicker, Thirona
AU - Eshete, Mekonen A.
AU - Adeyemo, Wasiu L.
AU - Hetmanski, Jacqueline B.
AU - Zeng, Erliang
AU - Adamson, Olawale
AU - Adeleke, Chinyere
AU - Li, Mary
AU - Sule, Veronica
AU - Kayali, Sami
AU - Olotu, Joy
AU - Mossey, Peter A.
AU - Obiri-Yeboah, Solomon
AU - Buxo, Carmen J.
AU - Beaty, Terri
AU - Taub, Margaret
AU - Donkor, Peter
AU - Marazita, Mary L.
AU - Odukoya, Oluwakemi
AU - Adeyemo, Adebowale A.
AU - Murray, Jeffrey C.
AU - Prince, Anya
AU - Butali, Azeez
N1 - Copyright:
© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - ACMG guideline
KW - orofacial clefts
KW - secondary findings
KW - sub-Saharan Africa
KW - whole genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85165906216&partnerID=8YFLogxK
U2 - 10.1002/mgg3.2237
DO - 10.1002/mgg3.2237
M3 - Article
C2 - 37496383
SN - 2324-9269
VL - 11
JO - Molecular Genetics and Genomic Medicine
JF - Molecular Genetics and Genomic Medicine
IS - 10
M1 - e2237
ER -