CILD5 is an autosomal recessive disorder characterized by early onset of a progressive decline in lung function due to an inability to clear mucus and particles from the airways. Affected individuals have recurrent infections of the sinuses, ears, ... CILD5 is an autosomal recessive disorder characterized by early onset of a progressive decline in lung function due to an inability to clear mucus and particles from the airways. Affected individuals have recurrent infections of the sinuses, ears, airways, and lungs. Sperm motility is also decreased. Individuals with CILD5 do not have situs inversus (summary by Olbrich et al., 2012).
Jeganathan et al. (2004) studied 7 families from the Faroe Islands segregating primary ciliary dyskinesia. Only 1 of the 11 affected family members had situs inversus. Electron microscopy of 1 patient showed an ultrastructural phenotype of absent outer ... Jeganathan et al. (2004) studied 7 families from the Faroe Islands segregating primary ciliary dyskinesia. Only 1 of the 11 affected family members had situs inversus. Electron microscopy of 1 patient showed an ultrastructural phenotype of absent outer dynein arms. Some of the patients had previously been reported by Ellerman and Bisgaard (1997) as having a progressive decline in lung function. Olbrich et al. (2012) reported follow-up of 3 of the families from the Faroe Islands with primary ciliary dyskinesia originally reported by Jeganathan et al. (2004): families UCL96, UCL109, and UCL139. They were not immediately consanguineous; however, they originated from a historically isolated population, and an ancestral relationship between the paternal grandparent of UCL109 and the maternal grandparent of UCL96 was verbally reported by the families. All patients presented in infancy or early childhood with respiratory insufficiency, chronic wet cough, chronic bronchitis, chronic rhinosinusitis, and otitis media; most developed bronchiectasis. None had situs inversus. Olbrich et al. (2012) also reported a consanguineous German family in which 3 sibs had CILD without situs inversus. All had onset of respiratory distress in early infancy. Other features included chronic wet cough, recurrent bronchitis, pneumonia, otitis media, chronic rhinosinusitis, and bronchiectasis. Transmission electron microscopy (TEM) of patient respiratory cilia showed that most exhibited a normal 9+2 axonemal composition, with 9 outer microtubule doublets surrounding 2 single central microtubules, and both outer and inner dynein arms showed no abnormalities. There were rare occurrences of 9+0 and 8+1 cilia, but most cross-sections appeared entirely normal. Thus, routine TEM findings were nonspecific and not sufficient for diagnosis of CILD. However, imaging with the higher resolution electron microscopy tomography showed that projection C2b was absent at the central pair (CP) apparatus. High-speed videomicroscopy of respiratory cilia and sperm flagella showed markedly reduced coordination of beating activity, reduced beating amplitudes, and reduced bending capacity; some immotile cilia were also observed. Mutant cilia did not generate distinct effective or recovery strokes and had a reduced capacity to transport mucus or particles, consistent with the defect in airway clearance observed in affected individuals. Olbrich et al. (2012) noted that the lack of situs inversus in patients with HYDIN mutations is consistent with the specific defect of the CP apparatus, which is not needed for cilia function of the embryonic node.
In 3 sibs, born of consanguineous German parents (family OP-305), with primary ciliary dyskinesia-5 without situs inversus, Olbrich et al. (2012) identified a homozygous splice site mutation in the HYDIN gene (610812.0001). The mutation was found by homozygosity ... In 3 sibs, born of consanguineous German parents (family OP-305), with primary ciliary dyskinesia-5 without situs inversus, Olbrich et al. (2012) identified a homozygous splice site mutation in the HYDIN gene (610812.0001). The mutation was found by homozygosity mapping followed by candidate gene sequencing. Olbrich et al. (2012) also identified a homozygous truncating mutation in HYDIN (K307X; 610812.0002) in 6 affected individuals from 3 families with CILD5 without situs inversus, all originating from the Faroe Islands (Jeganathan et al., 2004). The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing in 2 sibs from 1 family (UCL109), and was not found in several exome databases. Haplotype analysis indicated a founder effect in these 3 families. The findings were consistent with a loss of function. In a 48-year-old man from a consanguineous family of European descent who had been diagnosed with both retinitis pigmentosa (615434) and primary ciliary dyskinesia, Davidson et al. (2013) identified homozygosity for a splice site mutation in the HYDIN gene (610812.0003) as well as homozygosity for a missense mutation in the ARL2BP gene (M45R; 615407.0002). The patient had recurrent chest infections and respiratory failure from an early age and required physiotherapy regularly through the school years. He had a lifelong chronic 'wet cough,' and CT scan showed bronchiectasis of both lower lung lobes and the lingula, with the most severe disease in the right middle lobe. He had chronic nasal congestion, with a nasal nitric oxide screening test of 5 ppb (normal range, 400-1,000 ppb). Recurrent bouts of otitis media resulted in progressive conductive hearing loss, and he also had reduced sperm motility. Electron microscopy of nasal epithelial cells confirmed the absence of the C2B projection of the motile cilia. In addition, the patient developed difficulty with night vision in his 20s, evaluation of which led to a diagnosis of retinitis pigmentosa. There was no family history of any of these conditions. - Genetic Heterogeneity Olbrich et al. (2012) stated that the K307X mutation accounted for 3 of 8 families with CILD from the Faroe Islands, indicating genetic heterogeneity within this population.