BMPR2 Mutation in a Patient With Pulmonary Arterial Hypertension and Suspected Hereditary Hemorrhagic Telangiectasia
BMPR2 Mutation in a Patient With Pulmonary Arterial Hypertension and Suspected Hereditary Hemorrhagic Telangiectasia
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DOI：
10.1002/ajmg.a.32468
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发表时间：
2008-10-01
影响因子：
2
通讯作者：
Aldred, Micheala A.
中科院分区：
文献类型：
--
作者：
Rigelsky, Christina M.;Jennings, Constance;Aldred, Micheala A.
肺动脉高压（PAH）和遗传性出血性毛细血管扩张（HHT）是由编码TGF β /BMP超家族成员基因的种系突变引起的不同的临床实体：PAH中的BMPR2和HHT中的ACVRL1、ENG或SMAD4。当PAH和HHT偶尔在同一家族中共存时，ACVRL1突变占主导地位。我们报告一位36岁的女性，在24岁时被诊断为PAH。35岁大咯血后，发现多发肺动静脉畸形，提示对HHT的评估。基于鼻毛细血管扩张和鼻出血的其他发现，她符合库拉索岛疑似HHT的诊断标准。ACVRL1、ENG和SMAD4的突变分析正常，但发现BMPR2的种系无义模仿。这是首次报道与BMPR2突变相关的HHT特征，特别是肺部avm。它进一步强调了PAH和HHT的共同分子发病机制，并强调BMPR2基因分析适用于HHT和PAH患者。(c) 2008 Wiley-Liss, Inc。
Pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT) are distinct clinical entities caused by germline mutations in genes encoding members of the TGF beta/BMP superfamily: BMPR2 in PAH and ACVRL1, ENG, or SMAD4 in HHT. When PAH and HHT occasionally co-exist within the same family, ACVRL1 mutations predominate. We report a 36-year-old woman initially diagnosed with PAH at age 24. At 35, following massive hemoptysis, multiple pulmonary arteriovenous malformations were discovered, prompting evaluation for HHT. She met the Curacao diagnostic criteria for suspected HHT based on additional findings of nasal telangiectases and epistaxis. mutation analysis of ACVRL1, ENG, and SMAD4 was normal, but a germline nonsense imitation in BMPR2 was identified. This is the first known report of HHT features, particularly pulmonary AVMs, associated with a BMPR2 mutation. It adds further weight to a common molecular pathogenesis in PAH and HHT, and highlights that BMPR2 gene analysis is indicated in patients affected with both HHT and PAH. (c) 2008 Wiley-Liss, Inc.