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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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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. |
format | Online Article Text |
id | pubmed-10568375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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