#617092
Table of Contents
A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-35 (CILD35) is caused by homozygous mutation in the TTC25 gene (ODAD4; 617095) on chromosome 17q21.
Primary ciliary dyskinesia-35 (CILD35) is an autosomal recessive disorder characterized by recurrent upper and lower respiratory infections due to defective ciliary function. Examination of respiratory cilia shows lack of outer dynein arms (ODAs) and immotile cilia. Some patients may have laterality defects (summary by Wallmeier et al., 2016).
For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Wallmeier et al. (2016) reported 3 patients from 2 unrelated families with CILD35. The patients had typical respiratory symptoms beginning soon after birth, with recurrent upper and lower airway disease including chronic rhinitis, chronic otitis, chronic sinusitis, nasal polyps, chronic productive cough, recurrent pneumonia, and bronchiectasis. Nasal nitric oxide production was decreased. Two patients had laterality defects: one had situs inversus and the other had situs ambiguus. Patient respiratory epithelial cells showed normal ciliary 9+2 architecture and no evidence of tubular disorganization, but cross-sections of respiratory cilia showed absence of ODAs. Videomicroscopy showed that patient respiratory cilia were immotile, with only some showing residual flickery movement. There was no evidence of fewer or shortened cilia in patient respiratory epithelial cells.
The transmission pattern of CILD35 in the families reported by Wallmeier et al. (2016) was consistent with autosomal recessive inheritance.
In 3 patients from 2 unrelated families with CILD35, Wallmeier et al. (2016) identified 2 different homozygous loss-of-function mutations in the TTC25 gene (617095.0001 and 617095.0002). The mutations were found by a combination of homozygosity mapping and whole-exome sequencing.
Wallmeier et al. (2016) used CRISPR/Cas9 to generate mice with a deletion of exons 2 and 3 of Ttc25. Most mutant mice presented with small body size and some with hydrocephalus at 2 weeks of age. Most mutant animals had laterality defects. Deviation from mendelian distribution suggested that some Ttc25 mutant mice died prenatally. Mutant mice exhibited immotile nodal cilia and missing leftward flow by particle image velocimetry. Transmission electron microscopy demonstrated that cilia from mutant mice lacked ODAs and the ODA docking complex (ODA-DC).
Wallmeier, J., Shiratori, H., Dougherty, G. W., Edelbusch, C., Hjeij, R., Loges, N. T., Menchen, T., Olbrich, H., Pennekamp, P., Raidt, J., Werner, C., Minegishi, K., and 12 others. TTC25 deficiency results in defects of the outer dynein arm docking machinery and primary ciliary dyskinesia with left-right body asymmetry randomization. Am. J. Hum. Genet. 99: 460-469, 2016. [PubMed: 27486780, images, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 244; DO: 0110620;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q21.2 | Ciliary dyskinesia, primary, 35 | 617092 | Autosomal recessive | 3 | ODAD4 | 617095 |
A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-35 (CILD35) is caused by homozygous mutation in the TTC25 gene (ODAD4; 617095) on chromosome 17q21.
Primary ciliary dyskinesia-35 (CILD35) is an autosomal recessive disorder characterized by recurrent upper and lower respiratory infections due to defective ciliary function. Examination of respiratory cilia shows lack of outer dynein arms (ODAs) and immotile cilia. Some patients may have laterality defects (summary by Wallmeier et al., 2016).
For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Wallmeier et al. (2016) reported 3 patients from 2 unrelated families with CILD35. The patients had typical respiratory symptoms beginning soon after birth, with recurrent upper and lower airway disease including chronic rhinitis, chronic otitis, chronic sinusitis, nasal polyps, chronic productive cough, recurrent pneumonia, and bronchiectasis. Nasal nitric oxide production was decreased. Two patients had laterality defects: one had situs inversus and the other had situs ambiguus. Patient respiratory epithelial cells showed normal ciliary 9+2 architecture and no evidence of tubular disorganization, but cross-sections of respiratory cilia showed absence of ODAs. Videomicroscopy showed that patient respiratory cilia were immotile, with only some showing residual flickery movement. There was no evidence of fewer or shortened cilia in patient respiratory epithelial cells.
The transmission pattern of CILD35 in the families reported by Wallmeier et al. (2016) was consistent with autosomal recessive inheritance.
In 3 patients from 2 unrelated families with CILD35, Wallmeier et al. (2016) identified 2 different homozygous loss-of-function mutations in the TTC25 gene (617095.0001 and 617095.0002). The mutations were found by a combination of homozygosity mapping and whole-exome sequencing.
Wallmeier et al. (2016) used CRISPR/Cas9 to generate mice with a deletion of exons 2 and 3 of Ttc25. Most mutant mice presented with small body size and some with hydrocephalus at 2 weeks of age. Most mutant animals had laterality defects. Deviation from mendelian distribution suggested that some Ttc25 mutant mice died prenatally. Mutant mice exhibited immotile nodal cilia and missing leftward flow by particle image velocimetry. Transmission electron microscopy demonstrated that cilia from mutant mice lacked ODAs and the ODA docking complex (ODA-DC).
Wallmeier, J., Shiratori, H., Dougherty, G. W., Edelbusch, C., Hjeij, R., Loges, N. T., Menchen, T., Olbrich, H., Pennekamp, P., Raidt, J., Werner, C., Minegishi, K., and 12 others. TTC25 deficiency results in defects of the outer dynein arm docking machinery and primary ciliary dyskinesia with left-right body asymmetry randomization. Am. J. Hum. Genet. 99: 460-469, 2016. [PubMed: 27486780] [Full Text: https://doi.org/10.1016/j.ajhg.2016.06.014]
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