SNP Array Screening and Long Range PCR-Based Targeted Next Generation Sequencing for Autosomal Recessive Disease with Consanguinity: Insight from a Case of Xeroderma Pigmentosum Group C.

具有血缘关系的常染色体隐性遗传病的 SNP 阵列筛选和基于远程 PCR 的靶向下一代测序 ： 来自着色性干皮病 C 组病例的见解

• 影响指数: 4.141
• 发表时间: 2023 11 15
• 来源期刊: Genes (Basel)
• DOI: 10.3390/genes14112079
• PMID: 38003022
• 文章类型: Case Reports
• 中科院分区: Q2
• 方向: 生物
• 作者列表: Nomura F,Shimizu A,Togi S,Ura H,Niida Y

关键词: SNP array; autosomal recessive; consanguinity; isodisomy; long range PCR-based NGS; xeroderma pigmentosum group C

Mesh: Humans; Xeroderma Pigmentosum / diagnosis genetics epidemiology; Consanguinity; High-Throughput Nucleotide Sequencing; Polymerase Chain Reaction

Abstract

Advances in genetic technologies have made genetic testing more accessible than ever before. However, depending on national, regional, legal, and health insurance circumstances, testing procedures may still need to be streamlined in real-world clinical practice. In cases of autosomal recessive disease with consanguinity, the mutation locus is necessarily isodisomy because both alleles originate from a common ancestral chromosome. Based on this premise, we implemented integrated genetic diagnostic methods using SNP array screening and long range PCR-based targeted NGS in a Japanese patient with xeroderma pigmentosum (XP) under the limitation of the national health insurance system. SNP array results showed isodisomy only in XPC and ERCC4 loci. NGS, with a minimal set of long-range PCR primers, detected a homozygous frameshift mutation in XPC; NM_004628.5:c.218_219insT p.(Lys73AsnfsTer9), confirmed by Sanger sequencing, leading to a rapid diagnosis of XP group C. This shortcut strategy is applicable to all autosomal recessive diseases caused by consanguineous marriages, especially in scenarios with a moderate number of genes to test, a common occurrence in clinical genetic practice.

摘要

基因技术的进步使基因检测比以往任何时候都更容易获得。然而,取决于国家，区域,legal,和健康保险情况，在现实世界的临床实践中，测试程序可能仍然需要简化。在具有血缘关系的常染色体隐性疾病的情况下，突变位点必然是等分体，因为两个等位基因都来自一个共同的祖先染色体。基于这个前提,在国家健康保险制度的限制下,我们在1例患有着色性干皮病(XP)的日本患者中使用SNP阵列筛查和基于远程PCR的靶向NGS实施了综合遗传诊断方法.SNP阵列结果仅在XPC和ERCC4基因座中显示等分体。NGS,用最小的一套长程PCR引物，在XPC中检测到纯合移码突变；NM_004628.5：c.218_219insTp.（Lys73AsnfsTer9），经Sanger测序证实,导致XP组C的快速诊断。这种捷径策略适用于所有由近亲婚姻引起的常染色体隐性遗传疾病，尤其是在需要测试中等数量基因的情况下，在临床遗传学实践中很常见。