Primary ciliary dyskinesia-22 is an autosomal recessive disorder caused by defective structure and function of cilia or flagella. Ciliary dysfunction causes respiratory distress in term neonates, impaired mucociliary clearance, chronic cough, sinusitis, bronchiectasis, and male infertility. Defective motility ... Primary ciliary dyskinesia-22 is an autosomal recessive disorder caused by defective structure and function of cilia or flagella. Ciliary dysfunction causes respiratory distress in term neonates, impaired mucociliary clearance, chronic cough, sinusitis, bronchiectasis, and male infertility. Defective motility of embryonic nodal cilia leads to situs abnormalities in about 50% of patients. CILD22 is characterized by defects of the inner and outer dynein arms (summary by Zariwala et al., 2013).
Moore et al. (2013) reported 10 patients from 6 unrelated families with CILD22. Patients presented in infancy or early childhood with recurrent respiratory infections, persistent rhinosinusitis, otitis media, chronic cough, and variable presence of situs abnormalities. Light microscopy ... Moore et al. (2013) reported 10 patients from 6 unrelated families with CILD22. Patients presented in infancy or early childhood with recurrent respiratory infections, persistent rhinosinusitis, otitis media, chronic cough, and variable presence of situs abnormalities. Light microscopy of respiratory cilia showed a range of motility defects: some were static, whereas others showed slow, asynchronous beating. Electron microscopy showed either complete absence of the inner and outer dynein arms or decreased numbers of inner and outer dynein arms with reduced arm lengths.
In affected members of 14 families with primary ciliary dyskinesia-22, Zariwala et al. (2013) identified 11 different homozygous or compound heterozygous mutations in the ZMYND10 gene (see, e.g., 607070.0001-607070.0004). The initial mutation was found by homozygosity mapping combined ... In affected members of 14 families with primary ciliary dyskinesia-22, Zariwala et al. (2013) identified 11 different homozygous or compound heterozygous mutations in the ZMYND10 gene (see, e.g., 607070.0001-607070.0004). The initial mutation was found by homozygosity mapping combined with whole-exome sequencing in an Israeli individual with situs inversus. The subsequent mutations were found by sequencing the ZMYND10 gene in 300 patients with CILD. Transmission electron microscopy of respiratory ciliary epithelial samples from affected individuals showed a lack of outer and inner dynein arms on the ciliary axonemes, and immunofluorescence studies showed absence of the inner-arm protein DNALI1 (602135) and the outer-arm protein DNAH5 (603335). Moore et al. (2013) identified biallelic mutations in the ZMYND10 gene (see, e.g., 607070.0001; 607070.0005-607070.0006) in 6 (16%) of 38 families with CILD characterized by inner and outer dynein arm defects on ultrastructural analysis of respiratory epithelial cells. The initial mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. The mutations segregated with the disorder in the families. Most patients had a loss of inner and outer dynein arms from the cilia, but those with the missense mutation V16G (607070.0001) had an apparently intermediate phenotype with variable retention of the inner and outer dynein arms. Video microscopy of most patients showed cilia that were almost completely static, but 1 patient with the V16G mutation had cilia with a slowed and stiff beating pattern.