三个原发性淋巴水肿家族中已知淋巴水肿相关基因突变呈阴性的基因中的突变。

Mutations in the Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes.

作者信息

Ricci Maurizio, Compagna Rita, Amato Bruno, Kenanoglu Sercan, Veselenyiova Dominika, Kurti Danjela, Baglivo Mirko, Basha Syed Hussain, Serrani Roberta, Miggiano Giacinto Abele Donato, Aquilanti Barbara, Matera Giuseppina, Marceddu Giuseppe, Velluti Valeria, Gagliardi Lucilla, Dundar Munis, Krajcovic Juraj, Bertelli Matteo

机构信息

Division of Rehabilitation Medicine, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Italy.

Department of Public Health, University of Naples Federico II, Naples, Italy.

出版信息

Int J Genomics. 2020 Aug 25;2020:3781791. doi: 10.1155/2020/3781791. eCollection 2020.

DOI:10.1155/2020/3781791

PMID:32908855

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7468673/

Abstract

BACKGROUND

ARAP3 is a small GTPase-activating protein regulator, which has important functions in lymphatic vessel organogenesis and modulation of cell adhesion and migration. Mutations in the gene are associated with impaired lymphatic vessel formation.

OBJECTIVE

The aim of our study was to determine the genotypes of lymphedema patients in relation to variants in the gene in order to explore its role in the development of lymphedema.

METHODS AND RESULTS

We applied next-generation sequencing to DNA samples of a cohort of 246 Italian patients with lymphatic malformations. When we tested probands for known lymphedema genes, 235 out of 246 were negative. Retrospectively, we tested the DNA of these 235 patients for new candidate lymphedema-associated genes, including . Three out of 235 probands proved to carry rare missense heterozygous variants in . In the case of two families, other family members were also tested and proved negative for the variant, besides being unaffected by lymphedema. According to analysis, alterations due to these variants have a significant impact on the overall structure and stability of the resulting proteins.

CONCLUSIONS

Based on our results, we propose that variants in could be included in genetic testing for lymphedema.

摘要

背景

ARAP3是一种小GTP酶激活蛋白调节剂，在淋巴管器官发生以及细胞黏附和迁移的调节中具有重要功能。该基因的突变与淋巴管形成受损有关。

目的

我们研究的目的是确定淋巴水肿患者与该基因变异相关的基因型，以探讨其在淋巴水肿发生发展中的作用。

方法与结果

我们对一组246例意大利淋巴管畸形患者的DNA样本应用了二代测序技术。当我们检测先证者是否存在已知的淋巴水肿基因时，246例中有235例为阴性。回顾性地，我们检测了这235例患者的DNA，以寻找新的与淋巴水肿相关的候选基因，包括该基因。235例先证者中有3例被证明携带该基因罕见的错义杂合变异。在两个家族的病例中，除了未受淋巴水肿影响外，其他家庭成员也进行了检测，结果显示该变异为阴性。根据分析，这些变异导致的改变对所产生蛋白质的整体结构和稳定性有显著影响。