Ciliary Dyskinesia, Primary, 33
A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-33 (CILD33) is caused by homozygous mutation in the GAS8 gene (605178) on chromosome 16q24.
DescriptionPrimary ciliary dyskinesia-33 is an autosomal recessive disorder characterized by recurrent upper and lower respiratory infections due to defective ciliary clearance and resulting in chronic lung disease. Some patients may have recurrent ear infections resulting in conductive hearing impairment. Examination of respiratory cilia shows subtle movement defects. Laterality defects have not been reported (summary by Olbrich et al., 2015).
For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Clinical FeaturesOlbrich et al. (2015) reported 3 unrelated patients with primary ciliary dyskinesia. All had recurrent infections of the upper and lower respiratory tracts since early childhood, resulting in bronchiectasis and chronic atelectasis. Additional symptoms included recurrent otitis media, sometimes resulting in conductive hearing impairment, and decreased nasal nitric oxide (NO) levels. None had laterality defects. One of the patients had 2 similarly affected sibs who were not available for study.
InheritanceThe transmission pattern of CILD33 in the families reported by Olbrich et al. (2015) was consistent with autosomal recessive inheritance.
Molecular GeneticsIn 3 unrelated patients with CILD33, Olbrich et al. (2015) identified 3 different homozygous truncating mutations in the GAS8 gene (605178.0001-605178.0003). The mutations were identified by exome sequencing and confirmed by Sanger sequencing. Patients respiratory cilia showed absence of the GAS8 protein, consistent with a loss of function.
Animal ModelColantonio et al. (2009) showed that gas8-null zebrafish embryos showed hydrocephalus, left-right axis defects, and abnormal otolith composition of the inner ear, consistent with ciliary beating defects.