Ciliary Dyskinesia, Primary, 17

A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-17 (CILD17) is caused by homozygous mutation in the CCDC103 gene (614677) on chromosome 17q21.

Description

Primary ciliary dyskinesia-17 is an autosomal recessive disorder characterized by early infantile onset of respiratory distress associated with a defect in the function of ciliary outer dynein arms. Situs inversus is variable (summary by Panizzi et al., 2012).

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

Clinical Features

Panizzi et al. (2012) reported 10 patients from 6 families with primary ciliary dyskinesia. Five of the families were consanguineous and of Pakistani origin, and 1 was nonconsanguineous and of German origin. Four of the Pakistani families had previously been reported by O'Callaghan et al. (2010) and resided in the U.K. The patients had classic features of the disorder, including recurrent upper and lower respiratory infections, sinusitis, bronchiectasis, and variable dextrocardia or situs inversus. Electron microscopy showed variable defects in the inner and outer dynein arms of cilia that differed even with a family. Videomicroscopy showed either complete cilia paralysis, reduced beat amplitude, or loss of beat coordination.

Inheritance

The transmission pattern of CILD17 in the families reported by Panizzi et al. (2012) was consistent with autosomal recessive inheritance.

Mapping

By whole-genome linkage analysis of 4 consanguineous Pakistani families with CILD and absent outer and inner dynein arms, Panizzi et al. (2012) identified a locus on chromosome 17q12-q22 (maximum lod score of 4.8). The candidate region spanned 14 cM.

Molecular Genetics

In 10 patients from 6 families with CILD17, Panizzi et al. (2012) identified 1 of 2 homozygous mutations in the CCDC103 gene: 383delG (614677.0001) or H154P (614677.0002).