Primary ciliary dyskinesia-23 is an autosomal recessive disorder resulting from defective ciliary motility. Affected individuals have respiratory distress and recurrent upper and lower airway infections, and they often develop bronchiectasis. About 50% of patients have situs inversus or ... Primary ciliary dyskinesia-23 is an autosomal recessive disorder resulting from defective ciliary motility. Affected individuals have respiratory distress and recurrent upper and lower airway infections, and they often develop bronchiectasis. About 50% of patients have situs inversus or laterality defects. Ultrastructural analysis of respiratory cilia shows defects in the outer dynein arm (summary by Hjeij et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see 244400.
Hjeij et al. (2013) reported 12 patients from 10 families with CILD. All affected individuals had recurrent upper and lower airway disease as well as bronchiectasis. Seven of 12 individuals had neonatal respiratory distress syndrome. In addition, 8 ... Hjeij et al. (2013) reported 12 patients from 10 families with CILD. All affected individuals had recurrent upper and lower airway disease as well as bronchiectasis. Seven of 12 individuals had neonatal respiratory distress syndrome. In addition, 8 of the 12 affected individuals had situs inversus totalis and 4 had situs solitus. All tested individuals had low levels of nasal nitric oxide.
In 12 patients from 10 families with CILD23, Hjeij et al. (2013) identified homozygous or compound heterozygous mutations in the ARMC4 gene (see, e.g., 615408.0001-615408.0004). The first mutation, which was a deletion, was found by copy number variation ... In 12 patients from 10 families with CILD23, Hjeij et al. (2013) identified homozygous or compound heterozygous mutations in the ARMC4 gene (see, e.g., 615408.0001-615408.0004). The first mutation, which was a deletion, was found by copy number variation analysis of candidate genes from the ciliary proteome, and the subsequent mutations were found by targeted sequencing of 135 CILD patients with outer dynein arm defects. Overall, there was 1 deletion, 6 mutations resulting in premature stop codons, and 1 missense mutation. Respiratory cells from patients with truncating mutations showed absence of ARMC4 localization in the ciliary axonemes, and video microscopy showed either markedly reduced ciliary beat frequency and amplitude or complete immotility, consistent with severe outer dynein arm defects. Transmission electron microscopy of these cilia showed a marked reduction of outer dynein arms, but not a complete loss of axonemal outer dynein arm assembly. Immunofluorescence studies showed absence of DNAH5 (603335) and DNAI2 (605483) from the distal ciliary axonemes, indicating partial defects of the outer dynein arms. In these studies, cilia from patients with the missense mutation (L927W; 615408.0002) showed less severe anomalies, consistent with partial retention of protein function.