原发性睫状体运动障碍
纤毛
生物
轴丝
运动纤毛
动力蛋白
倒位
遗传学
超微结构
卡塔格综合征
纤毛形成
无义突变
鞭毛内运输
突变
细胞生物学
分子生物学
错义突变
解剖
支气管扩张
微管
基因
鞭毛
内科学
肺
医学
作者
Georg C. Schwabe,Katrin Hoffmann,Niki T. Loges,Daniel Birker,Colette Rossier,M. M. De Santi,Heike Olbrich,Manfred Fliegauf,Mike Failly,Uta Liebers,Mirella Collura,Gerhard Gaedicke,Stefan Mundlos,Ulrich Wahn,Jean‐Louis Blouin,B. Niggemann,Heymut Omran,Stylianos E. Antonarakis,Lucia Bartoloni
出处
期刊:Human Mutation
[Wiley]
日期:2008-02-01
卷期号:29 (2): 289-298
被引量:218
摘要
Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by perturbed or absent beating of motile cilia, which is referred to as Kartagener syndrome (KS) when associated with situs inversus. We present a German family in which five individuals have PCD and one has KS. PCD was confirmed by analysis of native and cultured respiratory ciliated epithelia with high-speed video microscopy. Respiratory ciliated cells from the affected individuals showed an abnormal nonflexible beating pattern with a reduced cilium bending capacity and a hyperkinetic beat. Interestingly, the axonemal ultrastructure of these respiratory cilia was normal and outer dynein arms were intact, as shown by electron microscopy and immunohistochemistry. Microsatellite analysis indicated genetic linkage to the dynein heavy chain DNAH11 on chromosome 7p21. All affected individuals carried the compound heterozygous DNAH11 mutations c.12384C>G and c.13552_13608del. Both mutations are located in the C-terminal domain and predict a truncated DNAH11 protein (p.Y4128X, p.A4518_A4523delinsQ). The mutations described here were not present in a cohort of 96 PCD patients. In conclusion, our findings support the view that DNAH11 mutations indeed cause PCD and KS, and that the reported DNAH11 nonsense mutations are associated with a normal axonemal ultrastructure and are compatible with normal male fertility. Hum Mutat 29(2), 289–298, 2008. © 2007 Wiley-Liss, Inc.
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