A novel pathogenic germline chromosome 3 inversion in von Hippel-Lindau disease.

IF 3.5 2区 医学 Q2 GENETICS & HEREDITY Journal of Medical Genetics Pub Date : 2024-10-23 DOI:10.1136/jmg-2024-110202
Cathy D Vocke, Christopher J Ricketts, Svetlana Pack, Mark Raffeld, Stephen Hewitt, Alexandra P Lebensohn, Lidenys O'Brien, Rabindra Gautam, Krista Reynolds, Laura S Schmidt, Kristin Choo, Alex Kenigsberg, Sandeep Gurram, Emily Y Chew, Naris Nilubol, Prashant Chittaboina, Maria J Merino, Mark W Ball, W Marston Linehan
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Abstract

von Hippel-Lindau (VHL) is an autosomal-dominant hereditary tumour susceptibility disease associated with pathogenic germline variants in the VHL tumour suppressor gene. VHL patients are at increased risk of developing multiple benign and malignant tumours. Current CLIA-based genetic tests demonstrate a very high detection rate of germline VHL variants in patients with clinical manifestations of VHL. In this report, we describe a large family with canonical VHL manifestations, for which no germline alteration had been detected by conventional germline testing. We identified a novel 291 kb chromosomal inversion involving chromosome 3p in affected family members. This inversion disrupts the VHL gene between exon 2 and exon 3 and is thereby responsible for the disease observed in this family.

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von Hippel-Lindau 病的新型致病基因 3 号染色体倒位。
von Hippel-Lindau(VHL)是一种常染色体显性遗传性肿瘤易感病,与 VHL 肿瘤抑制基因的致病性种系变异有关。VHL 患者罹患多种良性和恶性肿瘤的风险增加。目前基于 CLIA 的基因检测显示,在有 VHL 临床表现的患者中,种系 VHL 变异的检出率非常高。在本报告中,我们描述了一个具有典型 VHL 表现的大家庭,传统的种系检测并未发现其种系变异。我们在受影响的家族成员中发现了一个涉及 3p 染色体的新型 291 kb 染色体倒位。这种倒位破坏了外显子 2 和外显子 3 之间的 VHL 基因,从而导致了在该家族中观察到的疾病。
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来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
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