Hypertension and Brachydactyly Syndrome Associated With Vertebral Artery Malformation Caused by a PDE3A Missense Mutation
Hypertension and Brachydactyly Syndrome Associated With Vertebral Artery Malformation Caused by a PDE3A Missense Mutation
复制标题
与 PDE3A 错义突变引起的椎动脉畸形相关的高血压和短指综合征
DOI：
10.1093/ajh/hpz151
复制
发表时间：
2019-09
影响因子：
4.9
通讯作者：
Xian-Liang Zhou
中科院分区：
文献类型：
--
作者：
Peng Fan;Di Zhang;Kun-Qi Yang;Qiong-Yu Zhang;Fang Luo;Ying Lou;Ya-Xin Liu;Hui-Min Zhang;Lei Song;Jun Cai;Hai-Ying Wu;Xian-Liang Zhou
高血压和短指综合征（Hypertension and brachydactyly syndrome，HTNB），又称Bilginturan综合征，是一种罕见的常染色体显性遗传疾病，其特征是严重的盐非依赖性高血压、身材矮小、短指，如果不治疗，在50岁之前死于中风。本研究的目的是确定一个中国家庭的PDE3A突变导致HTNB相关的椎动脉畸形。方法收集所有受试者的外周血，提取DNA。进行下一代测序和桑格测序以鉴定PDE 3A突变。在PDE3A突变引起的HTNB先证者中进行比较概述。结果HTNB先证者的PDE3A基因存在一个错义突变c.1346G>A。该突变导致p.Gly449Asp，位于一个高度保守的结构域，并通过不同的生物信息学工具预测为破坏性的。共分离分析显示先证者遗传了其父亲的突变。先证者降压治疗有效。HTNB先证者与9个不同的PDE3A突变的比较概述揭示了表型异质性。结论遗传筛查可显著提高HTNB的早期诊断率。我们的研究不仅增加了中国人群中PDE3A突变的谱，并将HTNB患者的表型扩展到包括椎骨畸形，而且提高了对HTNB患者发病机制的认识。我们强调抗高血压治疗和长期随访对预防中风和不良心血管事件的重要性。
Abstract BACKGROUND Hypertension and brachydactyly syndrome (HTNB), also called Bilginturan syndrome, is a rare autosomal dominant disorder characterized by severe salt-independent hypertension, a short stature, brachydactyly, and death from stroke before the age of 50 years when untreated. The purpose of the present study was to identify a PDE3A mutation leading to HTNB associated with vertebral artery malformation in a Chinese family. METHODS Peripheral blood samples were collected from all subjects for DNA extraction. Next-generation sequencing and Sanger sequencing were performed to identify the PDE3A mutation. A comparative overview was performed in the probands with HTNB caused by PDE3A mutations. RESULTS Genetic analysis identified a missense mutation in PDE3A, c.1346G>A, in the proband with HTNB. This mutation, resulting in p.Gly449Asp, was located in a highly conserved domain and predicted to be damaging by different bioinformatics tools. Cosegregation analyses showed that the proband inherited the identified mutation from her father. Antihypertensive therapy was effective for the proband. Comparative overview of HTNB probands with 9 different PDE3A mutations revealed phenotypic heterogeneity. CONCLUSIONS Genetic screening can significantly improve the diagnosis of HTNB patients at an early age. Our study not only adds to the spectrum of PDE3A mutations in the Chinese population and extends the phenotype of HTNB patients to include vertebral malformation but also improves the awareness of pathogenesis in HTNB patients. We emphasize the importance of antihypertensive treatment and long-term follow-up to prevent stroke and adverse cardiovascular events.
登录
查看更多内容
影响因子：
14.9
作者：
Hou H;Zhao F;Zhou L;Zhu E;Teng H;Li X;Bao Q;Wu J;Sun Z
通讯作者：
Sun Z
DOI：
10.1038/gim.2017.159
发表时间：
2018-06
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Hauer NN;Popp B;Schoeller E;Schuhmann S;Heath KE;Hisado-Oliva A;Klinger P;Kraus C;Trautmann U;Zenker M;Zweier C;Wiesener A;Abou Jamra R;Kunstmann E;Wieczorek D;Uebe S;Ferrazzi F;Büttner C;Ekici AB;Rauch A;Sticht H;Dörr HG;Reis A;Thiel CT
通讯作者：
Thiel CT
影响因子：
30.8
作者：
H. Schuster;T. Wienker;S. Bähring;N. Bilginturan;Hakan R Toka;H. Neitzel;Eva Jeschke;O. Toka;Dennis A Gilbert;A. Lowe;J. Ott;H. Haller;F. Luft
通讯作者：
H. Schuster;T. Wienker;S. Bähring;N. Bilginturan;Hakan R Toka;H. Neitzel;Eva Jeschke;O. Toka;Dennis A Gilbert;A. Lowe;J. Ott;H. Haller;F. Luft
影响因子：
3
作者：
M. Litwin;E. Jurkiewicz;K. Nowak;A. Kościesza;R. Grenda;K. Malczyk;I. Kościesza
通讯作者：
M. Litwin;E. Jurkiewicz;K. Nowak;A. Kościesza;R. Grenda;K. Malczyk;I. Kościesza
影响因子：
15.9
作者：
Maass, Philipp G.;Rump, Andreas;Baehring, Sylvia
通讯作者：
Baehring, Sylvia