Mobile Element Insertion in the APOB Exon 3 Coding Sequence: A New Challenge in Hypobetalipoproteinemia Diagnosis.

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Clinical Genetics Pub Date : 2024-11-25 DOI:10.1111/cge.14655

Laurie Surles, Alexandre Janin, Corentin Molitor, Nicolas Chatron, Myriam Moret, Séverine Nony, Sabrina Dumont, Oriane Marmontel, Thomas Simonet, Agnès Sassolas, Philippe Moulin, Mathilde Di Filippo

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引用次数: 0

Abstract

Mobile elements (ME) can transpose by copy-and-paste mechanisms. A heterozygous insertion in APOB exon 3 coding sequence was suspected in a patient with hypobetalipoproteinemia (HBL), by gel electrophoresis of the PCR products. An insertion of a 85 bp fragment flanked by a polyA stretch and a target replication site duplication was identified as a ME insertion (MEI) from the AluYa5 subfamily, NM_000384.3(APOB):c.135_136ins(160). Then, the DNA was reanalyzed using our NGS custom panel. Routine analysis did not reveal any causative variant, but manual inspection of the alignments and MELT enabled us to detect this MEI from NGS data. A functional study revealed that this MEI introduces a stop codon p.(Phe46Alafs*2) and additionally leads to p.(Lys41Serfs*2) due to an exon skipping. This is the first report of a MEI into APOB, as a cause of HBL. Furthermore, our study highlights the value of including MEI-callers in routine pipelines to improve primary dyslipidemia diagnosis.

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APOB 第 3 外显子编码序列中的移动元素插入：低脂蛋白血症诊断的新挑战

移动元素（ME）可以通过复制粘贴机制进行转座。通过对 PCR 产物进行凝胶电泳，怀疑一名低脂蛋白血症（HBL）患者的 APOB 第 3 外显子编码序列中存在杂合插入。经鉴定，一个85 bp的插入片段侧翼有一个polyA片段和一个目标复制位点复制片段，是来自AluYa5亚家族的ME插入（MEI），NM_000384.3(APOB):c.135_136ins(160)。然后，使用我们的 NGS 定制面板对 DNA 进行了重新分析。常规分析没有发现任何致病变异，但通过人工检查比对和 MELT，我们从 NGS 数据中检测到了这个 MEI。功能研究显示，该 MEI 引入了一个终止密码子 p.(Phe46Alafs*2)，并由于外显子跳过而导致 p.(Lys41Serfs*2)。这是首次报道 APOB 中的 MEI 可导致 HBL。此外，我们的研究还凸显了将MEI-caller纳入常规管道以改善血脂异常初诊的价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Genetics 医学-遗传学

CiteScore

6.50

自引率

0.00%

发文量

175

审稿时长

3-8 weeks

期刊介绍： Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease