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

Autor: Oladayo A; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa, USA.; Iowa Institute for Oral Health Research, University of Iowa, Iowa City, Iowa, USA., Gowans LJJ; Iowa Institute for Oral Health Research, University of Iowa, Iowa City, Iowa, USA.; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Awotoye W; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa, USA.; Iowa Institute for Oral Health Research, University of Iowa, Iowa City, Iowa, USA., Alade A; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa, USA.; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA., Busch T; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa, USA., Naicker T; Department of Pediatrics, University of KwaZulu-Natal, Pinetown, South Africa., Eshete MA; School Medicine, Surgical Department, Addis Ababa University, Addis Ababa, Ethiopia., Adeyemo WL; Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, Nigeria., Hetmanski JB; Department of Epidemiology, School of Public Health Johns Hopkins University, Baltimore, Maryland, USA., Zeng E; Division of Biostatistics and Computational Biology, College of Dentistry, University of Iowa, Iowa City, Iowa, USA., Adamson O; Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, Nigeria., Adeleke C; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa, USA., Li M; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa, USA., Sule V; Department of Operative Dentistry, College of Dentistry, University of Iowa, Iowa City, Iowa, USA., Kayali S; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa, USA., Olotu J; Department of Anatomy, University of Port Harcourt, Port Harcourt, Nigeria., Mossey PA; Department of Orthodontics, University of Dundee, Dundee, UK., Obiri-Yeboah S; Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Buxo CJ; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico, USA., Beaty T; Department of Epidemiology, School of Public Health Johns Hopkins University, Baltimore, Maryland, USA., Taub M; Department of Epidemiology, School of Public Health Johns Hopkins University, Baltimore, Maryland, USA., Donkor P; Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Marazita ML; Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, and Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Odukoya O; Department of Community Health and Primary Care, College of Medicine, University of Lagos, Lagos, Nigeria., Adeyemo AA; National Human Genomic Research Institute, Bethesda, Maryland, USA., Murray JC; Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA., Prince A; College of Law, University of Iowa, Iowa City, Iowa, USA., Butali A; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa, USA.; Iowa Institute for Oral Health Research, University of Iowa, Iowa City, Iowa, USA.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2023 Oct; Vol. 11 (10), pp. e2237. Date of Electronic Publication: 2023 Jul 26.
DOI: 10.1002/mgg3.2237
Abstrakt: 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.
(© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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