Korosh Heydari - Ph.D. of Molecular Medicine, Genetics Medical laboratory, Shahrekord University of Medical Sciences
Ahoura Nozari - Ph.D. of Medical Genetics, Genetics Medical laboratory, Shahrekord University of Medical Sciences
Morteza Hashemzadeh - Ph.D. of Human Genetics. Professor of Medical, Head of Medical Genetic department, Milad Lab, Isfahan

Introduction: The immotile cilia syndrome (ICS) is a genetically disorder characterized by dysmotility or even complete immotility of the cilia in the airways and elsewhere. Kartagener syndrome is a subgroup of the ICS and is further characterized by situs inversus viscerum. Most authors estimate the prevalence of Kartagener syndrome at 1 in 30,000 to 1 in 60,000 persons. The ICS clearly is a genetically heterogeneous disease, although its clinical profile is fairly uniform. Many genes participate in the construction of a cilium, and an error in any one of them will prevent the cilia from working properly. Therefore, most clinical manifestations date from early childhood. The inheritance in most cases is autosomal recessive.In families in which the ICS occurs, on average, half the affected siblings have situs inversus. Usually spermatozoa are also either immotile or poorly motile, so males are typically sterile. Females may also be fertile or infertile. The diagnosis of ICS can be established by clinical phenotype and by ciliary ultrastructural analysis or molecular genetic testing. About two thirds of probands can be diagnosed by the presence of biallelic pathogenic variants in one of the 32 genes known to be associated with ICS.Method: We performed Whole Exome Sequencing (WES) for a 10 years old child with Karetagener syndrome from consanguine couple. The first symptoms emerged six months ago and then diagnosis based on clinical features was made. The couple showed secondary infertility due to father’s astenospermia. Moreover, three-generation pedigree exhibit several cases of infertility in both men and women. For recognizing mutated gene, variants were analyzed by autosomal recessive inheritance mode.Result: Eventually, by several filtering processes, a novel splice site mutation in DNAH11 gene (NM_001277115), exon5: c.883-1G> A, was identified as the most likely disease-susceptibility variant and then confirmed by Sanger sequencing in the family. The mutation frequency was checked out in the local databases.Conclusions: DNAH11 (Dynein, Axonemal, Heavy Chain 11) gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in Kartagener Syndrome and male sterility.