Loges et al. (2009) reported 3 unrelated patients with primary ciliary dyskinesia. Two had situs inversus totalis and severe lung disease; the third had situs solitus. Analysis of respiratory cilia showed immotile cilia due to a combined defect ... Loges et al. (2009) reported 3 unrelated patients with primary ciliary dyskinesia. Two had situs inversus totalis and severe lung disease; the third had situs solitus. Analysis of respiratory cilia showed immotile cilia due to a combined defect of both the inner and outer dynein arms. Duquesnoy et al. (2009) reported 5 patients from 4 unrelated families with primary ciliary dyskinesia. There were 2 males and 3 females. Three patients had situs inversus, and 2 females had fertility defects. All had airway disease, including bronchitis, sinusitis, otitis, and bronchiectasis. None had cilia beating in respiratory cells, and all showed complete absence of both inner and outer dynein arms on transmission electron microscopy.
In 3 probands with primary ciliary dyskinesia associated with combined inner and outer dynein arm defects, Loges et al. (2009) identified homozygous and compound heterozygous mutations in the LRRC50 gene (see, e.g., 613190.0001 and 613190.0002). One patient was ... In 3 probands with primary ciliary dyskinesia associated with combined inner and outer dynein arm defects, Loges et al. (2009) identified homozygous and compound heterozygous mutations in the LRRC50 gene (see, e.g., 613190.0001 and 613190.0002). One patient was homozygous for a truncating mutation, 1 was compound heterozygous for larger deletions involving LRRC50 and several neighboring genes, and 1 was compound heterozygous for a deletion and truncation mutation. Functional analysis showed that LRRC50 deficiency resulted in disrupted assembly of DNAH5 (603335)- and DNAI2 (605483)-containing outer dynein arms, as well as DNALI1 (602135)-containing inner dynein arm complexes, resulting in immotile cilia in respiratory cells. Duquesnoy et al. (2009) identified 6 different heterozygous mutations in the LRRC50 gene (see, e.g., 613190.0003-613190.0004) in 3 unrelated patients with CILD13, as well as a homozygous mutation (L175R; 613190.0005) in 2 sibs with CILD13. All mutations led to a loss of function, and all patients had absence of both the inner and outer dynein arms.