Balanced Translocation Disrupting JAG1 Identified by Optical Genomic Mapping in Suspected Alagille Syndrome

IF 3.3 2区医学 Q2 GENETICS & HEREDITY

Human Mutation Pub Date : 2023-06-08 DOI:10.1155/2023/5396281

Yi-Qiong Zhang, Peng-Fei Gao, Jing-Min Yang, Jing Zhang, Yu-Lan Lu, Jian-She Wang

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Abstract

We report the clinical and genetic features of a Han Chinese boy who presented with disease suspect for Alagille syndrome (ALGS). Multiple genetic analyses (panel sequencing, multiplex-ligation-dependent probe amplification, and whole genome sequencing) failed to uncover a causative variant. Optical genomic mapping detected a reciprocal translocation between chromosomes 4 and 20, interrupting JAG1. Long-range polymerase chain reaction and targeted sequencing identified the exact breakpoints. Sanger sequencing and reanalysis of genome sequencing raw data further confirmed the result. This translocation is expected to generate aberrant JAG1 transcripts that lead to complete loss of JAG1 expression. This is the first t(4;20)(q22.1;p12.2) balanced translocation detected by optical genomic mapping and characterized at base-pair resolution in ALGS. Our approach permitted precise diagnosis and genetic counseling.

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通过光学基因组定位鉴定疑似Alagille综合征的平衡易位干扰JAG1

我们报告了一名中国汉族男孩的临床和遗传特征，他出现了Alagille综合征（ALGS）的疑似疾病。多重基因分析（面板测序、多重连接依赖性探针扩增和全基因组测序）未能发现致病变体。光学基因组图谱检测到4号和20号染色体之间的相互易位，中断了JAG1。远程聚合酶链式反应和靶向测序确定了确切的断点。桑格测序和基因组测序原始数据的再分析进一步证实了这一结果。这种易位预计会产生异常的JAG1转录物，导致JAG1表达的完全丧失。这是通过光学基因组定位检测到的第一个t（4；20）（q22.1；p12.2）平衡易位，并在ALGS中以碱基对分辨率进行了表征。我们的方法允许精确的诊断和基因咨询。

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来源期刊

Human Mutation 医学-遗传学

CiteScore

8.40

自引率

5.10%

发文量

190

审稿时长

2 months

期刊介绍： Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.