Abstract
Primary ciliary dyskinesia (PCD) is a rare genetic disorder, which shows extensive genetic heterogeneity and is mostly inherited in an autosomal recessive fashion. There are four genes with a proven pathogenetic role in PCD. DNAH5 and DNAI1 are involved in 28 and 10% of PCD cases, respectively, while two other genes, DNAH11 and TXNDC3, have been identified as causal in one PCD family each. We have previously identified a 3.5 cM (2.82 Mb) region on chromosome 15q linked to Kartagener syndrome (KS), a subtype of PCD characterized by the randomization of body organ positioning. We have now refined the KS candidate region to a 1.8 Mb segment containing 18 known genes. The coding regions of these genes and three neighboring genes were subjected to sequence analysis in seven KS probands, and we were able to identify 60 single nucleotide sequence variants, 35 of which resided in mRNA coding sequences. However, none of the variations alone could explain the occurrence of the disease in these patients.
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Acknowledgements
We thank all the Polish and Slovak PCD families who participated in this study for their invaluable cooperation, and J Pawlik (Rabka, Poland) and A Kapellerova (Bratislava, Slovakia) for providing study material and clinical data. We gratefully acknowledge the help of Ewa Rutkiewicz in collecting biological material, of Jackie Senior in editing the manuscript and of Behrooz Alizadeh in interpreting the statistical data. This research was partly financed by Grant PBZ-KBN-122/P05-1 from the Polish Ministry of Science and Higher Education. MG is supported by the International PhD Program of the University of Utrecht.
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Geremek, M., Schoenmaker, F., Zietkiewicz, E. et al. Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q. Eur J Hum Genet 16, 688–695 (2008). https://doi.org/10.1038/ejhg.2008.5
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DOI: https://doi.org/10.1038/ejhg.2008.5
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