Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome)
Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome)
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DOI：
10.1086/319511
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发表时间：
2001-04-01
影响因子：
9.8
通讯作者：
Bouvagnet, P
中科院分区：
文献类型：
--
作者：
Guichard, C;Harricane, MC;Bouvagnet, P
Kartagener综合征（KS）是一种症状三联征（鼻息肉、支气管扩张和完全性内脏逆位），与覆盖上下呼吸道的上皮细胞纤毛和精子鞭毛的超微结构异常有关。轴丝动力蛋白中间链基因1（DNAI1），这已被证明是负责的情况下，原发性纤毛运动障碍（PCD）无逆位，进行了筛选的突变在一系列的34例KS患者。我们在三名独立的患者和他们的两名兄弟姐妹中鉴定了复合杂合DNAI 1基因缺陷，这些患者表现为PCD和孤立部位（即，内脏的正常位置）。引人注目的是，这五名患者共有一个突变等位基因（剪接缺陷），这与其他地方报道的PCD患者中发现的突变DNAI1等位基因之一相同。最后，本研究证明了睫状体功能与部位确定之间的联系，因为DNA I 1中的复合突变杂合性导致了具有孤立部位或反位部位（KS）的PCD。
Kartagener syndrome (KS) is a trilogy of symptoms (nasal polyps, bronchiectasis, and situs inversus totalis) that is associated with ultrastructural anomalies of cilia of epithelial cells covering the upper and lower respiratory tracts and spermatozoa flagellae. The axonemal dynein intermediate-chain gene 1 (DNAI1), which has been demonstrated to be responsible for a case of primary ciliary dyskinesia (PCD) without situs inversus, was screened for mutation in a series of 34 patients with KS. We identified compound heterozygous DNAI1 gene defects in three independent patients and in two of their siblings who presented with PCD and situs solitus (i.e., normal position of inner organs). Strikingly, these five patients share one mutant allele (splice defect), which is identical to one of the mutant DNAI1 alleles found in the patient with PCD, reported elsewhere. Finally, this study demonstrates a link between ciliary function and situs determination, since compound mutation heterozygosity in DNAI1 results in PCD with situs solitus or situs inversus (KS).