Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused byDNAH11mutations
| Autor: | Ulrich Wahn, Mirella Collura, Niki Tomas Loges, Manfred Fliegauf, Jean-Louis Blouin, Stefan Mundlos, Stylianos E. Antonarakis, Heymut Omran, Heike Olbrich, M. Margherita de Santi, Katrin Hoffmann, Daniel Birker, Bodo Niggemann, Uta Liebers, Georg C. Schwabe, Lucia Bartoloni, Colette Rossier, Gerhard Gaedicke, Mike Failly |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Axoneme Adolescent Mutation/genetics Molecular Sequence Data Dynein Nonsense mutation Cilia/ultrastructure Video microscopy Biology Polymorphism Single Nucleotide Epithelial Cells/metabolism/pathology Mutant Proteins/chemistry otorhinolaryngologic diseases Genetics medicine Humans ddc:576.5 Axoneme/ultrastructure Cilia Amino Acid Sequence Alleles Genetics (clinical) Primary ciliary dyskinesia Dynein ATPase/chemistry/genetics/metabolism Kartagener Syndrome Cilium Dyneins Infant Epithelial Cells Axonemal Dyneins Middle Aged Polymorphism Single Nucleotide/genetics medicine.disease Immunohistochemistry Molecular biology Pedigree Phenotype Mutation Motile cilium Mutant Proteins Female Kartagener Syndrome/genetics |
| Zdroj: | Human Mutation, Vol. 29, No 2 (2008) pp. 289-98 |
| ISSN: | 1098-1004 1059-7794 |
| DOI: | 10.1002/humu.20656 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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