Ciliary Dyskinesia, Primary, 34

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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-34 (CILD34) is caused by homozygous mutation in the DNAJB13 gene (610263) on chromosome 11q13.

Description

Primary ciliary dyskinesia-34 (CILD34) is an autosomal recessive disorder characterized by childhood onset of recurrent sinopulmonary infections due to impaired ciliary function. Affected males are infertile due to impaired sperm function and viability. Laterality defects have not been observed in this type of CILD (summary by El Khouri et al., 2016).

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

Clinical Features

El Khouri et al. (2016) reported an adult brother and sister, born of consanguineous parents, with primary ciliary dyskinesia diagnosed in their fifties. Both had recurrent respiratory infections, including bronchiectasis, rhinosinusitis, and otitis, that began in childhood. Nasal nitric oxide was very low. Transmission electron microscopy of nasal biopsy respiratory cilia showed multiple cilia lacking central microtubules, including mainly cilia with a '9+0' pattern. Videomicroscopy showed decreased ciliary beating frequency compared to controls, and the beating pattern was abnormal. The man was infertile due to severe oligo-astheno-terato-zoospermia and necrozoospermia. Total sperm count and viability were severely decreased. An unrelated 14-year-old girl with CILD had a similar disorder: she had low nasal nitric oxide, but studies of nasal and bronchial biopsies were inconclusive because of the very low number of cilia. None of the patients had laterality defects.

Inheritance

The transmission pattern of CILD34 in the families reported by El Khouri et al. (2016) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 3 patients from 2 unrelated families with CILD34, El Khouri et al. (2016) identified 2 different homozygous loss-of-function mutations in the DNAJB13 gene (610263.0001 and 610263.0002). The mutations were found by exome sequencing. One mutation resulted in a truncated protein, whereas the other was a missense mutation that resulted in undetectable DNAJB13 levels in patient samples, consistent with a loss of function. Transmission electron microscopy analysis of patient respiratory cilia showed an abnormal percentage of cilia lacking central microtubules, indicating that DNAJB13 is critical for upholding the integrity of the central complex in motile cilia and flagella.