The immotile cilia syndrome (ICS) is a genetically determined disorder characterized by dysmotility or immotility of the cilia in airway epithelial cells, spermatozoa and other ciliated cells of the body. Kartagener syndrome (KS) is a subgroup of ICS characterized by a classic triad of symptoms: situs inversus, bronchiectasis and chronic sinusitis. Ciliary immotility is caused by various ultrastructural defects of cilia, predominantly by a lack of dynein arms. The clinical consequences of KS include pronounced craniofacial manifestations. In FY94 a large scale collaborative genetic epidemiology study of KS was planned with Dr. Michael Witt in Poznan, Poland. Over the next 12 months sixty Polish families with at least one child affected with KS will be recruited for this study. Coded DNA samples and research medical records will be sent to MEDIB, NIDR, NIH laboratory for genotyping. To facilitate large scale genetic mapping of the human genome we will apply microsatellite markers suitable for use with a fluorescence-based automated DNA fragment analyzer. They are arranged into 29 sets, covering 22 autosome and the X chromosome, with an average interval of 10cM. Each set consists of 12-17 marker loci, with allele size ranges that do not overlap. Marker loci were selected on the basis of their reliability in PCR, polymorphism content, map position and the accuracy with which alleles can be scored automatically by the Genotypes(TM) program. Classic pair wise linkage analyses using the program MENDEL which calculates the LOD score for complex diseases will be conducted in MEDIB. Multipoint linkage analyses will also be performed by calculating location scores using the programs LINKAGE and MENDEL.
| Witt, M; Wang, Y f; Wang, S et al. (1999) Exclusion of chromosome 7 for Kartagener syndrome but suggestion of linkage in families with other forms of primary ciliary dyskinesia. Am J Hum Genet 64:313-8 |
