At least 6.3% of patients with PCD have heterotaxy, and most of those have cardiovascular abnormalities. The prevalence of congenital heart disease with heterotaxy is 200-fold higher in PCD than in the general population (1:50 versus 1:10 000); thus, patients with PCD should have cardiac evaluation. Conversely, mutations in genes that adversely affect both respiratory and embryological nodal cilia are a significant cause of heterotaxy and congenital heart disease, and screening for PCD is indicated in those patients.

Viral haemorrhagic septicaemia (VHS) caused by the rhabdovirus VHSV is economically the most important viral disease in European rainbow trout farming. Until 1989, this virus was mainly isolated from freshwater salmonids but in the last decade, it has also been isolated from an increasing number of free-living marine fish species. To study the genetic evolution of VHSV, the entire G gene from 74 isolates was analysed. VHSV from wild marine species caught in the Baltic Sea, Skagerrak, Kattegat, North Sea, and English Channel and European freshwater isolates, appeared to share a recent common ancestor. Based on the estimated nucleotide substitution rate, the ancestor of the European fresh water isolates was dated some 50 years ago. This finding fits with the initial reports in the 1950s on clinical observations of VHS in Danish freshwater rainbow trout farms. The study also indicates that European marine VHSV and the North American marine line separated approx. 500 years ago. The codon substitution rate among the freshwater VHSV isolates was found to be 2?5 times faster than among marine isolates. The data support the hypothesis of the marine environment being the original reservoir of VHSV and that the change in host range (to include rainbow trout) may have occurred several times. Virus from the marine environment will therefore continue to represent a threat to the trout aquaculture industry.

Rationale: Primary ciliary dyskinesia (PCD) is characterized by recurrent airway infections and randomization of left-right body asymmetry. To date, autosomal recessive mutations have only been identified in a small number of patients involving DNAI1 and DNAH5, which encode outer dynein arm components. Methods: We screened 109 white PCD families originating from Europe and North America for presence of DNAH5 mutations by haplotype analyses and/or sequencing. Results: Haplotype analyses excluded linkage in 26 families. In 30 PCD families, we identified 33 novel (12 nonsense, 8 frameshift, 5 splicing, and 8 missense mutations) and two known DNAH5 mutations. We observed clustering of mutations within five exons harboring 27 mutant alleles (52%) of the 52 detected mutant alleles. Interestingly, 6 (32%) of 19 PCD families with DNAH5 mutations from North America carry the novel founder mutation 10815delT. Electron microscopic analyses in 22 patients with PCD with mutations invariably detected outer dynein arm ciliary defects. Highresolution immunofluorescence imaging of respiratory epithelial cells from eight patients with DNAH5 mutations showed mislocalization of mutant DNAH5 and accumulation at the microtubule organizing centers. Mutant DNAH5 was absent throughout the ciliary axoneme in seven patients and remained detectable in the proximal ciliary axoneme in one patient carrying compound heterozygous splicing mutations at the 3-end (IVS75-2AϾT, IVS76ϩ5GϾA). In a preselected subpopulation with documented outer dynein arm defects (n ϭ 47), DNAH5 mutations were identified in 53% of patients. Conclusions: DNAH5 is frequently mutated in patients with PCD exhibiting outer dynein arm defects and mutations cluster in five exons.

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