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

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 d...

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Autores principales: Oladayo, Abimbola, Gowans, Lord Jephthah Joojo, Awotoye, Waheed, Alade, Azeez, Busch, Tamara, Naicker, Thirona, Eshete, Mekonen A., Adeyemo, Wasiu L., Hetmanski, Jacqueline B., Zeng, Erliang, Adamson, Olawale, Adeleke, Chinyere, Li, Mary, Sule, Veronica, Kayali, Sami, Olotu, Joy, Mossey, Peter A., Obiri‐Yeboah, Solomon, Buxo, Carmen J., Beaty, Terri, Taub, Margaret, Donkor, Peter, Marazita, Mary L., Odukoya, Oluwakemi, Adeyemo, Adebowale A., Murray, Jeffrey C., Prince, Anya, Butali, Azeez
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568375/
https://www.ncbi.nlm.nih.gov/pubmed/37496383
http://dx.doi.org/10.1002/mgg3.2237
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author Oladayo, Abimbola
Gowans, Lord Jephthah Joojo
Awotoye, Waheed
Alade, Azeez
Busch, Tamara
Naicker, Thirona
Eshete, Mekonen A.
Adeyemo, Wasiu L.
Hetmanski, Jacqueline B.
Zeng, Erliang
Adamson, Olawale
Adeleke, Chinyere
Li, Mary
Sule, Veronica
Kayali, Sami
Olotu, Joy
Mossey, Peter A.
Obiri‐Yeboah, Solomon
Buxo, Carmen J.
Beaty, Terri
Taub, Margaret
Donkor, Peter
Marazita, Mary L.
Odukoya, Oluwakemi
Adeyemo, Adebowale A.
Murray, Jeffrey C.
Prince, Anya
Butali, Azeez
author_facet Oladayo, Abimbola
Gowans, Lord Jephthah Joojo
Awotoye, Waheed
Alade, Azeez
Busch, Tamara
Naicker, Thirona
Eshete, Mekonen A.
Adeyemo, Wasiu L.
Hetmanski, Jacqueline B.
Zeng, Erliang
Adamson, Olawale
Adeleke, Chinyere
Li, Mary
Sule, Veronica
Kayali, Sami
Olotu, Joy
Mossey, Peter A.
Obiri‐Yeboah, Solomon
Buxo, Carmen J.
Beaty, Terri
Taub, Margaret
Donkor, Peter
Marazita, Mary L.
Odukoya, Oluwakemi
Adeyemo, Adebowale A.
Murray, Jeffrey C.
Prince, Anya
Butali, Azeez
author_sort Oladayo, Abimbola
collection PubMed
description 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.
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spelling pubmed-105683752023-10-13 Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts Oladayo, Abimbola Gowans, Lord Jephthah Joojo Awotoye, Waheed Alade, Azeez Busch, Tamara Naicker, Thirona Eshete, Mekonen A. Adeyemo, Wasiu L. Hetmanski, Jacqueline B. Zeng, Erliang Adamson, Olawale Adeleke, Chinyere Li, Mary Sule, Veronica Kayali, Sami Olotu, Joy Mossey, Peter A. Obiri‐Yeboah, Solomon Buxo, Carmen J. Beaty, Terri Taub, Margaret Donkor, Peter Marazita, Mary L. Odukoya, Oluwakemi Adeyemo, Adebowale A. Murray, Jeffrey C. Prince, Anya Butali, Azeez Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2023-07-26 /pmc/articles/PMC10568375/ /pubmed/37496383 http://dx.doi.org/10.1002/mgg3.2237 Text en © 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Oladayo, Abimbola
Gowans, Lord Jephthah Joojo
Awotoye, Waheed
Alade, Azeez
Busch, Tamara
Naicker, Thirona
Eshete, Mekonen A.
Adeyemo, Wasiu L.
Hetmanski, Jacqueline B.
Zeng, Erliang
Adamson, Olawale
Adeleke, Chinyere
Li, Mary
Sule, Veronica
Kayali, Sami
Olotu, Joy
Mossey, Peter A.
Obiri‐Yeboah, Solomon
Buxo, Carmen J.
Beaty, Terri
Taub, Margaret
Donkor, Peter
Marazita, Mary L.
Odukoya, Oluwakemi
Adeyemo, Adebowale A.
Murray, Jeffrey C.
Prince, Anya
Butali, Azeez
Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts
title Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts
title_full Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts
title_fullStr Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts
title_full_unstemmed Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts
title_short Clinically actionable secondary findings in 130 triads from sub‐Saharan African families with non‐syndromic orofacial clefts
title_sort clinically actionable secondary findings in 130 triads from sub‐saharan african families with non‐syndromic orofacial clefts
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568375/
https://www.ncbi.nlm.nih.gov/pubmed/37496383
http://dx.doi.org/10.1002/mgg3.2237
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