Ciliary Dyskinesia, Primary, 32

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

DNAAF3, DRC1, DNAI1, CCDC151, ARMC4, FOXJ1, DNAAF4, CCDC40, RSPH1, CCDC114, DNAH9, ZMYND10, LRRC6, PIH1D3, CCDC65, CFAP300, CFAP221, DNAH1, CCDC103, RSPH3, TTC25, SPEF2, CFAP298, MCIDAS, HYDIN, DNAAF5, RPGR, SPAG1, GAS8, STK36, OFD1, GAS2L2, CCNO, DNAH5, LRRC56, DNAJB13, DNAH11, CCDC39, DNAI2, SLIT2, AP1B1, C1orf127, RSPH9, NME8, PCBD1, DNAAF1, RSPH4A, AK7, CDO1, DNAH6, CFTR, SIT1, TCTE3, MBL2, RFX1, NME7, TXN, TEKT1, DNAL1, NME5, WDR19, DNAH7, CHD7, DPCD, CDON, NTM, ACVR2B

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A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-32 (CILD32) is caused by homozygous or compound heterozygous mutation in the RSPH3 gene (615876) on chromosome 6q25.

Description

Primary ciliary dyskinesia-32 is an autosomal recessive disorder caused by defective structure and function of cilia. Ciliary dysfunction causes respiratory distress in term neonates, impaired mucociliary clearance, chronic respiratory infections, bronchiectasis, and infertility. The ciliary defect affects the central pair complex and radial spokes of the 9+2 motile cilia; affected individuals do not have situs abnormalities (summary by Jeanson et al., 2015).

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

Clinical Features

Jeanson et al. (2015) reported 5 unrelated patients, ranging in age from 12 to 52 years, with primary ciliary dyskinesia. All had significant airway disease, including a history of neonatal respiratory distress, bronchiectasis, rhinosinusitis, and otitis. Nasal nitric oxide levels, assessed in 3 patients, were low. An older man and an older woman were both infertile. None of the patients had situs inversus or laterality defects. Analysis of cilia showed an increased percentage of cilia with absence of 1 or both central pair microtubules, disorganized cilia, and cilia with decreased or absent radial spokes. Videomicroscopy showed some immotile cilia as well as cilia with decreased or abnormal beat frequency.

Inheritance

The transmission pattern of CILD32 in the families reported by Jeanson et al. (2015) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 5 unrelated patients with CILD32, Jeanson et al. (2015) identified homozygous or compound heterozygous mutations in the RSPH3 gene (615876.0001-615876.0005). The mutations in the first patient were found by homozygosity mapping and whole-exome sequencing; mutations in the subsequent patients were found by screening the RSPH3 gene in 30 affected individuals with primary ciliary dyskinesia associated with central complex defects who had no mutations in the RSPH1 (609314), RSPH4A (612647), or RSPH9 (612648) genes. Overall, RSPH3 mutations were found in 5 (10.4%) of 48 patients with CILD due to central complex or radial spoke defects.