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Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations
Author(s) -
Schwabe Georg C.,
Hoffmann Katrin,
Loges Niki Tomas,
Birker Daniel,
Rossier Colette,
de Santi Margherita M.,
Olbrich Heike,
Fliegauf Manfred,
Failly Mike,
Liebers Uta,
Collura Mirella,
Gaedicke Gerhard,
Mundlos Stefan,
Wahn Ulrich,
Blouin JeanLouis,
Niggemann Bodo,
Omran Heymut,
Antonarakis Stylianos E.,
Bartoloni Lucia
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20656
Subject(s) - primary ciliary dyskinesia , cilium , biology , axoneme , motile cilium , dynein , situs inversus , ultrastructure , genetics , kartagener syndrome , nonsense mutation , intraflagellar transport , microbiology and biotechnology , mutation , missense mutation , anatomy , microtubule , gene , medicine , flagellum , bronchiectasis , lung
Abstract 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.