Ciliary Dyskinesia, Primary, 6

A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-6 (CILD6) is caused by mutation in the TXNDC3 gene (NME8; 607421) on chromosome 7p14. One such patient has been reported.

For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).

Clinical Features

Duriez et al. (2007) reported a 13-year-old girl with primary ciliary dyskinesia. She had chronic respiratory infections with bronchiectasis, chronic sinusitis, and serous otitis. She also had situs ambiguus with the heart and the liver located centrally. Electron microscopy showed that 66% of her respiratory cilia had shortened or absent outer dynein arms. The authors reported a unrelated patient who also had chronic respiratory infections with bronchiectasis, chronic sinusitis, and serous otitis, but he had situs inversus totalis. Electron microscopy of his respiratory cilia showed no ultrastructural defect of the respiratory cilia, but 40% were immotile.

Molecular Genetics

In a girl with primary ciliary dyskinesia, Duriez et al. (2007) identified 2 variants in the TXNDC3 gene: one was a pathogenic mutation (607421.0001) and the other a single-nucleotide polymorphism (SNP) in a splice site (607421.0002), which was shown to affect alternative splicing of the gene. Each unaffected parent was heterozygous for 1 of the TXNDC3 variants. Duriez et al. (2007) emphasized the unusual molecular mechanism underlying this mendelian autosomal recessive disorder, which is a SNP-induced modification of the ratio of 2 functional isoforms generated by alternative splicing. An unrelated patient was heterozygous for the splice site variant, which was of undetermined significance.