Mutations in DNAH5 account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia
Mutations in DNAH5 account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia
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DOI：
10.1136/jmg.2008.061176
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发表时间：
2009-04-01
影响因子：
4
通讯作者：
Blouin, J-L
中科院分区：
文献类型：
--
作者：
Failly, M.;Bartoloni, L.;Blouin, J-L
背景：原发性睫状肌运动障碍(PCD)的特征是上呼吸道(鼻、支气管和额窦)反复感染和左右身体不对称的随机性。到目前为止，PCD主要是常染色体隐性遗传，已发现5个基因突变：动力蛋白臂蛋白亚基DNAI1、DNAH5和DNAH11、激酶TXNDC3和X-连锁视网膜色素变性GTP酶调节基因RPGR。方法：采用变性高效液相色谱(DHPLC)和测序技术对89例PCD患者进行DNAH5基因编码区和剪接区的突变筛查。患者主要来自欧洲，在没有任何表型预选的情况下被招募。结果：我们鉴定了18个新的(无义、剪接、小缺失和错义)和6个先前描述的突变。有趣的是，这些DNAH5突变主要与外+内动力蛋白手臂超微结构缺陷有关(50%)。结论：总的来说，在我们的临床异质性队列中，15%的患者发现了DNAH5的这两个等位基因的突变。尽管大多数患者的基因改变仍未确定，但DNAH5已确定主要的PCD基因。
Background: Primary ciliary dyskinesia (PCD) is characterised by recurrent infections of the upper respiratory airways (nose, bronchi, and frontal sinuses) and randomisation of left-right body asymmetry. To date, PCD is mainly described with autosomal recessive inheritance and mutations have been found in five genes: the dynein arm protein subunits DNAI1, DNAH5 and DNAH11, the kinase TXNDC3, and the X-linked retinitis pigmentosa GTPase regulator RPGR.Methods: We screened 89 unrelated individuals with PCD for mutations in the coding and splice site regions of the gene DNAH5 by denaturing high performance liquid chromatography (DHPLC) and sequencing. Patients were mainly of European origin and were recruited without any phenotypic preselection.Results: We identified 18 novel (nonsense, splicing, small deletion and missense) and six previously described mutations. Interestingly, these DNAH5 mutations were mainly associated with outer + inner dyneins arm ultrastructural defects (50%).Conclusion: Overall, mutations on both alleles of DNAH5 were identified in 15% of our clinically heterogeneous cohort of patients. Although genetic alterations remain to be identified in most patients, DNAH5 is to date the main PCD gene.