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Hallazgos secundarios clínicamente procesables en 130 tríadas de familias del África subsahariana con hendiduras orofaciales no sindrómicas

Introduction: The frequency and implications of secondary findings (SFs) from genomic testing data have been extensively researched. Sin embargo, 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. Además, we filtered for four more genes (HBB, HSD32B, G6PD and ACADM).

Resultados: 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.

Keywords: ACMG guideline; hendiduras orofaciales; secondary findings; sub-Saharan Africa; whole genome sequencing.

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