生物谷：根據(jù)North Carolina大學(xué)Chapel Hill醫(yī)學(xué)院的科學(xué)家研究結(jié)果,，一種導(dǎo)致罕見(jiàn)呼吸道疾病的基因缺陷同時(shí)將導(dǎo)致一些先天性心臟病。
這種呼吸道疾病和纖毛有關(guān)，纖毛是一種幫助肺部清除粘液和灰塵等污染物的結(jié)構(gòu),。科學(xué)家首先發(fā)現(xiàn)在患有纖毛運(yùn)動(dòng)障礙（PCD）的兒童中存在這一聯(lián)系,。一種基因突變損傷了纖毛運(yùn)動(dòng),，從而導(dǎo)致PCD。而在UNC-Chapel Hill的一些PCD患兒同時(shí)患有先天性心臟病導(dǎo)致的心肺位置異常,。
小組因此懷疑這兩者間存在聯(lián)系,，因?yàn)榱硪环N纖毛在胚胎發(fā)育過(guò)程中負(fù)責(zé)探測(cè)及組織器官。結(jié)果發(fā)現(xiàn)在患有PCD的人群中,，同時(shí)患有心肺位置異常的幾率是常人的200倍（分別為1/50和1/10000）,。結(jié)果發(fā)表在6月5日的Circulation上。
文章主要作者肺部學(xué)教授Michael R. Knowles表示：“這表明醫(yī)生在治療心天性心臟病患者時(shí)同時(shí)要注意監(jiān)測(cè)肺部缺陷,。”
Knowles認(rèn)為,，患有心臟移位和先天性心臟病的兒童通常需要手術(shù)來(lái)進(jìn)行修復(fù)，而如果在術(shù)后存在呼吸道并發(fā)癥,，醫(yī)生會(huì)認(rèn)為這是心臟病造成的,。但新研究證明，這些呼吸道疾病同樣可能由基因缺陷導(dǎo)致,。
337位PCD患者中,，21位有心肺移位,。而科學(xué)家又對(duì)12位患有心肺移位的患者進(jìn)行了基因測(cè)試，結(jié)果其中7位存在導(dǎo)致PCD的兩個(gè)基因突變之一,。UNC的兒科臨床副教授Blair V. Robinson說(shuō)：“現(xiàn)在我們知道遇到類似心臟病患者時(shí),，需要同時(shí)檢查纖毛功能異常。其中的聯(lián)系將幫助我們更好的了解這些異常的原因,。”
（生物谷引自教育部科技發(fā)展中心）
英文原文鏈接：http://www.physorg.com/news100798002.html
原始出處:
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 [email protected]
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.
