生物谷：根据North Carolina大学Chapel Hill医学院的科学家研究结果，一种导致罕见呼吸道疾病的基因缺陷同时将导致一些先天性心脏病。
这种呼吸道疾病和纤毛有关，纤毛是一种帮助肺部清除粘液和灰尘等污染物的结构。科学家首先发现在患有纤毛运动障碍（PCD）的儿童中存在这一联系。一种基因突变损伤了纤毛运动，从而导致PCD。而在UNC-Chapel Hill的一些PCD患儿同时患有先天性心脏病导致的心肺位置异常。
小组因此怀疑这两者间存在联系，因为另一种纤毛在胚胎发育过程中负责探测及组织器官。结果发现在患有PCD的人群中，同时患有心肺位置异常的几率是常人的200倍（分别为1/50和1/10000）。结果发表在6月5日的Circulation上。
文章主要作者肺部学教授Michael R. Knowles表示：“这表明医生在治疗心天性心脏病患者时同时要注意监测肺部缺陷。”
Knowles认为，患有心脏移位和先天性心脏病的儿童通常需要手术来进行修复，而如果在术后存在呼吸道并发症，医生会认为这是心脏病造成的。但新研究证明，这些呼吸道疾病同样可能由基因缺陷导致。
337位PCD患者中，21位有心肺移位。而科学家又对12位患有心肺移位的患者进行了基因测试，结果其中7位存在导致PCD的两个基因突变之一。UNC的儿科临床副教授Blair V. Robinson说：“现在我们知道遇到类似心脏病患者时，需要同时检查纤毛功能异常。其中的联系将帮助我们更好的了解这些异常的原因。”
（生物谷引自教育部科技发展中心）
英文原文链接：http://www.physorg.com/news100798002.html
原始出处:
Published online before print May 21, 2007, doi:10.1161/CIRCULATIONAHA.106.649038
(Circulation. 2007;115:2814-2821.)
Congenital Heart Disease
Congenital Heart Disease and Other Heterotaxic Defects in a Large Cohort of Patients With Primary Ciliary Dyskinesia
Marcus P. Kennedy, MD; Heymut Omran, MD; Margaret W. Leigh, MD; Sharon Dell, MD; Lucy Morgan, MD; Paul L. Molina, MD; Blair V. Robinson, MD; Susan L. Minnix, RN; Heike Olbrich, PhD; Thomas Severin, MD; Peter Ahrens, MD; Lars Lange, MD; Hilda N. Morillas, MD; Peadar G. Noone, MD; Maimoona A. Zariwala, PhD; Michael R. Knowles, MD
From the University of North Carolina (M.P.K., M.W.L., P.L.M., B.V.R., S.L.M., H.N.M., P.G.N., M.A.Z., M.R.K.), Chapel Hill; University Hospital Freiburg (H. Omran, H. Olbrich, T.S.), Freiburg, Germany; The Toronto Hospital for Sick Children (S.D.), Toronto, Canada; Concord Hospital (L.M.), New South Wales, Australia; Darmstädter Kinderkliniken Prinzessin Margaret (P.A.), Darmstädt, Germany; and University Hospital Cologne (L.L.), Cologne, Germany.
Correspondence to Dr Michael R. Knowles, Cystic Fibrosis/Pulmonary Research and Treatment Center, 7019 Thurston Bowles Bldg, CB7248, Chapel Hill, NC 27599-7248. E-mail knowles@med.unc.edu
Received June 30, 2006; accepted February 22, 2007.
Background— Primary ciliary dyskinesia (PCD) is a recessive genetic disorder that is characterized by sinopulmonary disease and reflects abnormal ciliary structure and function. Situs inversus totalis occurs in 50% of PCD patients (Kartagener’s syndrome in PCD), and there are a few reports of PCD with heterotaxy (situs ambiguus), such as cardiovascular anomalies. Advances in diagnosis of PCD, such as genetic testing, allow the systematic investigation of this association.
Methods and Results— The prevalence of heterotaxic defects was determined in 337 PCD patients by retrospective review of radiographic and ultrasound data. Situs solitus (normal situs) and situs inversus totalis were identified in 46.0% and 47.7% of patients, respectively, and 6.3% (21 patients) had heterotaxy. As compared with patients with situs solitus, those with situs abnormalities had more ciliary outer dynein arm defects, fewer inner dynein arm and central apparatus defects (P<0.001), and more mutations in ciliary outer dynein arm genes (DNAI1 and DNAH5; P=0.022). Seven of 12 patients with heterotaxy who were genotyped had mutations in DNAI1 or DNAH5. Twelve patients with heterotaxy had cardiac and/or vascular abnormalities, and most (8 of 12 patients) had complex congenital heart disease.
Conclusions— At least 6.3% of patients with PCD have heterotaxy, and most of those have cardiovascular abnormalities. The prevalence of congenital heart disease with heterotaxy is 200-fold higher in PCD than in the general population (1:50 versus 1:10 000); thus, patients with PCD should have cardiac evaluation. Conversely, mutations in genes that adversely affect both respiratory and embryological nodal cilia are a significant cause of heterotaxy and congenital heart disease, and screening for PCD is indicated in those patients.
