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.
Mol Genet Genomic Med. 2023 Oct;11(10):e2237. doi: 10.1002/mgg3.2237. Epub 2023 Jul 26.
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.
简介:从基因组测试数据中发现的次要发现(SFs)的频率和意义已经得到了广泛的研究。然而,对于在大规模人群基因组研究中代表性不足的非洲人,SFs 的频率或报告情况知之甚少。由于第一个非洲人口口腔颌面裂全基因组测序数据的可用性,促使我们进行了这项研究。
方法:总共分析了 130 个病例-父母三体型的 SFs,这些 SFs 在 ACMG SFv.3.0 列表基因中。此外,我们还筛选了另外四个基因(HBB、HSD32B、G6PD 和 ACADM)。
结果:我们在 55 个基因中发现了 246 个独特的变异体;在四个基因中的五个变异体被归类为致病性或可能致病性(P/LP)。在 2.3%(9/390)的受试者中发现了 P/LP 变体,这一频率高于报告的多种族的 1%左右。在 ACMG 列表中,致病性变体在 PRKAG(p.Glu183Lys)中观察到。PALB2(p.Glu159Ter)、RYR1(p.Arg2163Leu)和 LDLR(p.Asn564Ser)基因中的变体被预测为 LP。
结论:本研究提供了非洲队列中 SFs 的频率和致病性的信息。早期风险检测将有助于减轻疾病负担,并有助于增加对不同人群中可操作基因组变异分布和影响的认识。
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