Primary ciliary dyskinesia-24 is an autosomal recessive disorder resulting from defects of motile cilia. It is characterized clinically by sinopulmonary infection and subfertility; situs inversus is not observed. Ultrastructural examination of mutant cilia shows defects of the central ... Primary ciliary dyskinesia-24 is an autosomal recessive disorder resulting from defects of motile cilia. It is characterized clinically by sinopulmonary infection and subfertility; situs inversus is not observed. Ultrastructural examination of mutant cilia shows defects of the central microtubule complex and radial spokes (summary by Kott et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see 244400.
Kott et al. (2013) reported 12 patients from 10 unrelated families with primary ciliary dyskinesia. Affected individuals had a sinopulmonary syndrome characterized by otitis, rhinosinusitis, bronchiectasis, chronic obstructive pulmonary disease, and, in some cases, neonatal respiratory distress. Four ... Kott et al. (2013) reported 12 patients from 10 unrelated families with primary ciliary dyskinesia. Affected individuals had a sinopulmonary syndrome characterized by otitis, rhinosinusitis, bronchiectasis, chronic obstructive pulmonary disease, and, in some cases, neonatal respiratory distress. Four patients studied, including 3 females and 1 male, had subfertility. None of the 12 patients had situs inversus. Cilia on patient respiratory epithelial cells showed variable abnormal beating patterns; motility in 1 patient was absent. Electron microscopy showed central microtubule complex and radial spoke defects in 19 to 70% of cilia. Some patients showed decreased nasal nitric oxide, but this was not a consistent finding.
In 12 patients from 10 families with CILD without situs inversus, Kott et al. (2013) identified 7 biallelic mutations in the RSPH1 gene (see, e.g., 609314.0001-609314.0005). The mutation in the first patient was found by a combination of ... In 12 patients from 10 families with CILD without situs inversus, Kott et al. (2013) identified 7 biallelic mutations in the RSPH1 gene (see, e.g., 609314.0001-609314.0005). The mutation in the first patient was found by a combination of homozygosity mapping and whole-exome sequencing. The subsequent mutations were found in patients from a larger cohort of 36 families with CILD and central complex and radial spoke defects. Respiratory cilia from 1 affected individual showed undetectable RSPH1 protein, consistent with a loss of function. RSPH1 mutations accounted for 20.8% of the 48 families studied with this specific phenotype. Kott et al. (2013) noted that patients with RSPH1 mutations do not have situs inversus because central complex defects do not affect the 9+0 structure of embryonic nodal cilia.