Primary ciliary dyskinesia (PCD) is a genetic disorder of motile cilia. Clinical features include chronic oto-sinopulmonary disease, laterality defects, and male fertility reflecting impaired function of respiratory cilia in the upper and lower respiratory tracts, nodal cilia in the embryonic node and sperm tails, respectively. Recent studies have identified over 40 PCD-associated genes that encode proteins involved in ciliary biogenesis, assembly, structure, or function. Mutations in these genes account for approximately 70% of PCD cases; therefore, further gene discovery is expected. The diagnosis of PCD is challenging because no single test has the required diagnostic accuracy. Recent efforts have focused on standardizing and validating a panel of tests (including assessment for key clinical features, nasal nitric oxide measurement, ciliary ultrastructure analysis, and PCD genetic testing) to be used at PCD Centers to accurately diagnose PCD. Multi-center research programs focused on PCD in North America and Europe have been crucial for PCD gene discovery, advancing our understanding of the natural history of PCD and launching multi-center clinical trials.

Background: Most methods for constructing aneuploid yeast strains that have gained a specific chromosome rely on spontaneous failures of cell division fidelity. In Saccharomyces cerevisiae, extra chromosomes can be obtained when errors in meiosis or mitosis lead to nondisjunction, or when nuclear breakdown occurs in heterokaryons. We describe a strategy for constructing N+1 disomes that does not require such spontaneous failures. The method combines two well-characterized genetic tools: a conditional centromere that transiently blocks disjunction of one specific chromosome, and a duplication marker assay that identifies disomes among daughter cells. To test the strategy, we targeted chromosomes III, IV, and VI for duplication.

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Background OFD1 has long been recognized as the gene implicated in the classic dysmorphology syndrome, oral‐facial‐digital syndrome type I (OFDSI). Over time, pathogenic variants in OFD1 were found to be associated with X‐linked intellectual disability, Joubert syndrome type 10 (JBTS10), Simpson‐Golabi‐Behmel syndrome type 2 (SGBS2), and retinitis pigmentosa. Recently, OFD1 pathogenic variants have been implicated in primary ciliary dyskinesia (PCD), a disorder of the motile cilia with a phenotype that includes recurrent oto‐sino‐pulmonary infections, situs abnormalities, and decreased fertility. Methods We describe three male patients with PCD who were found to have hemizygous pathogenic variants in OFD1, further supporting that PCD is part of a clinical spectrum of OFD1‐related disorders. In addition, we provide a review of the available clinical literature describing patients with OFD1 variants and highlight the phenotypic variability of OFD1‐related disease. Results Some individuals with hemizygous OFD1 variants have PCD, either apparently isolated or in combination with other features of OFD1‐related disorders. Conclusion As clinicians consider the presence or absence of conditions allelic at OFD1, PCD should be considered part of the spectrum of OFD1‐related disorders. Understanding the OFD1‐related disease spectrum may allow for more focused genetic testing and more timely management of treatable sequelae.