Ciliary Dyskinesia, Primary, 29

A number sign (#) is used with this entry because primary ciliary dyskinesia-29 (CILD29) is caused by homozygous or compound heterozygous mutation in the CCNO gene (607752) on chromosome 5q11.

Description

Primary ciliary dyskinesia-29 is an autosomal recessive disorder characterized by early childhood onset of recurrent respiratory infections due to defective mucociliary clearance. Patients do not have situs inversus (summary by Wallmeier et al., 2014).

For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see 244400.

Clinical Features

Wallmeier et al. (2014) reported 16 patients from 10 families who had recurrent upper and lower respiratory infections from early childhood. The disorder was progressive, resulting in bronchiectasis, chronic airway disease with atelectasis, mucus plugging, and deterioration of lung function. Two patients required lung transplantation as adults. Nasal nitric oxide was markedly reduced. One female presented with infertility and used assisted reproduction to become pregnant. None of the patients had situs inversus. Patient respiratory epithelial cells showed either a complete absence or markedly decreased numbers of cilia, and cultured patient respiratory epithelial cells showed a severe defect in generation of multiple motile cilia associated with insufficient centriole numbers and decreased basal bodies. Some basal bodies were mislocalized in the cytoplasm, suggesting a basal body migration defect. However, the few residual cilia that correctly expressed axonemal motor proteins were motile and did not exhibit obvious beating defects.

Casey et al. (2015) reported 2 brothers from a consanguineous Irish Traveller family (family B) with primary ciliary dyskinesia. Both presented with recurrent lower respiratory tract infections, and 1 also had recurrent otitis media. Nasal nitric oxide was decreased. Neither patient had situs inversus. Nasal respiratory epithelial cells were completely nude, suggesting ciliary aplasia, but this may have been secondary to active infection.

Inheritance

The transmission pattern of CILD29 in the families reported by Wallmeier et al. (2014) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 16 patients from 10 families with primary ciliary dyskinesia-29, Wallmeier et al. (2014) identified homozygous or compound heterozygous mutations in the CCNO gene (see, e.g., 607752.0001-607752.0006). All but 1 of the mutations resulted in a truncated protein, consistent with a loss of function. Several of the families were consanguineous and 1 was of Kuwaiti origin. The first mutation was found by whole-exome sequencing of 1 family, and the remaining families were identified from a cohort of 53 families with a similar phenotype. Studies of patient cells and in vitro studies suggested that CCNO functions in a pathway to promote mother centriole amplification and maturation in preparation for apical docking and ciliogenesis.

In 2 brothers of Irish Traveller descent with CILD29, Casey et al. (2015) identified a homozygous truncating mutation in the CCNO gene (607752.0002). The mutation, which was found by a combination of homozygosity mapping and exome variant analysis, was confirmed by Sanger sequencing. The mutation segregated with the disorder in the family.