Primary ciliary dyskinesia-19 is an autosomal recessive ciliopathy characterized by chronic sinopulmonary infections, asthenospermia, and immotile cilia. Respiratory epithelial cells and sperm flagella of affected individuals lack both the inner and outer dynein arms. About 50% of patients ... Primary ciliary dyskinesia-19 is an autosomal recessive ciliopathy characterized by chronic sinopulmonary infections, asthenospermia, and immotile cilia. Respiratory epithelial cells and sperm flagella of affected individuals lack both the inner and outer dynein arms. About 50% of patients have situs inversus (summary by Kott et al., 2012). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see 244400.
Kott et al. (2012) reported 6 patients from 5 unrelated European families with primary ciliary dyskinesia. All had early onset of chronic sinopulmonary infections, including bronchitis resulting in bronchiectasis, rhinosinusitis, and otitis. One patient had nasal polyps and ... Kott et al. (2012) reported 6 patients from 5 unrelated European families with primary ciliary dyskinesia. All had early onset of chronic sinopulmonary infections, including bronchitis resulting in bronchiectasis, rhinosinusitis, and otitis. One patient had nasal polyps and 2 had situs inversus. Nasal respiratory epithelial cells and spermatozoa showed immotile cilia or flagella, and ultrastructural analysis showed absence of both the inner and outer dynein arms of axonemes.
In 6 patients from 5 unrelated families of European descent with primary ciliary dyskinesia-19, Kott et al. (2012) identified biallelic mutations in the LRRC6 gene (614930.0001-614930.0005). The first mutation was identified by homozygosity mapping and candidate gene analysis ... In 6 patients from 5 unrelated families of European descent with primary ciliary dyskinesia-19, Kott et al. (2012) identified biallelic mutations in the LRRC6 gene (614930.0001-614930.0005). The first mutation was identified by homozygosity mapping and candidate gene analysis in an affected consanguineous family. The patients with CILD19 accounted for 5 (10.6%) of 47 families with a CILD phenotype characterized by absence of both inner and outer dynein arms. Kott et al. (2012) speculated that the LRRC6 gene plays a role with other proteins in the cytoplasmic preassembly of dynein arms. In 13 families with CILD19, Zariwala et al. (2013) identified 9 different homozygous or compound heterozygous mutations in the LRRC6 gene (see, e.g., 614930.0006 and 614930.0007). Five of the mutations were truncating. Patient respiratory samples showed defective ciliary outer and inner dynein arms on transmission electron microscopy, absence of the outer and inner arm proteins DNAH5 (603335) and DNALI1 (602135) from ciliary axonemes, and immotile cilia on video microscopy. Truncating mutations abrogated the interaction of LRRC6 with ZMYND10 (607070), whereas missense mutations did not.