Clinically actionable secondary findings in 130 triads from sub-Saharan African families with non-syndromic orofacial clefts.
ACMG guideline
orofacial clefts
secondary findings
sub-Saharan Africa
whole genome sequencing
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
23
05
2023
received:
30
01
2023
accepted:
28
06
2023
medline:
20
12
2023
pubmed:
27
7
2023
entrez:
27
7
2023
Statut:
ppublish
Résumé
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. 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). 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. 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.
Identifiants
pubmed: 37496383
doi: 10.1002/mgg3.2237
pmc: PMC10568375
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2237Subventions
Organisme : NIGMS NIH HHS
ID : U54 GM133807
Pays : United States
Organisme : NIDCR NIH HHS
ID : T90 DE023520
Pays : United States
Organisme : NIDCR NIH HHS
ID : R00 DE024571
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE028300
Pays : United States
Organisme : NIH HHS
ID : DE028300
Pays : United States
Informations de copyright
© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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