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撒哈拉以南非洲地区非综合征性口腔颌面裂家系中 130 对三体型中的临床可操作性次要发现。

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

机构信息

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.

出版信息

Mol Genet Genomic Med. 2023 Oct;11(10):e2237. doi: 10.1002/mgg3.2237. Epub 2023 Jul 26.


DOI:10.1002/mgg3.2237
PMID:37496383
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10568375/
Abstract

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.

摘要

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。

相似文献

[1]
Clinically actionable secondary findings in 130 triads from sub-Saharan African families with non-syndromic orofacial clefts.

Mol Genet Genomic Med. 2023-10

[2]
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Cleft Palate Craniofac J. 2018-5

[3]
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[4]
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[5]
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[6]
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[7]
Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations.

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[8]
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[9]
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Genes (Basel). 2023-3-7

[10]
Association between FOXE1 and non-syndromic orofacial clefts in a northeastern Chinese population.

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引用本文的文献

[1]
Perceptions and beliefs of community gatekeepers about genomic risk information in African cleft research.

BMC Public Health. 2024-2-17

本文引用的文献

[1]
Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate.

Sci Rep. 2022-7-11

[2]
ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG).

Genet Med. 2022-7

[3]
Whole Exome Sequencing in South Africa: Stakeholder Views on Return of Individual Research Results and Incidental Findings.

Front Genet. 2022-6-8

[4]
Variant landscape of the RYR1 gene based on whole genome sequencing of the Singaporean population.

Sci Rep. 2022-3-31

[5]
Genetic Susceptibility to Breast Cancer in Sub-Saharan African Populations.

JCO Glob Oncol. 2021-9

[6]
Actionable secondary findings in the 73 ACMG-recommended genes in 1559 Thai exomes.

J Hum Genet. 2022-3

[7]
The introduction of genetic counseling in Ethiopia: Results of a training workshop and lessons learned.

PLoS One. 2021

[8]
Frequency and management of medically actionable incidental findings from genome and exome sequencing data: a systematic review.

Physiol Genomics. 2021-9-1

[9]
Opportunities and barriers for genetic service delivery in Kenya from a health personnel perspective.

J Community Genet. 2021-10

[10]
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG).

Genet Med. 2021-8

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