Overview table of published PCD causing genes

PCD is a genetically heterogeneous disease, which is usually inherited in an autosomal recessive manner. For autosomal recessive PCD variants, so far 37 distinct genes have been discovered. PIH1D3 is located on the X chromosome, loss-of-function mutations cause PCD in males.

Component of the outer dynein arms (ODA)

Name Phenotype (ultrastructure) Situs inversus (~50%)
DNAI1 ODA-defect Yes
DNAI2 ODA-defect Yes
DNAH5 ODA-defect Yes
DNAH9 ODA-defect Yes
DNAH11 not detectable Yes
CCDC103 ODA-defect Yes
DNAL1 ODA-defect Yes
TXNDC3 (NME8) partial ODA-defect Yes

Component of the ODA docking complex

Name Phenotype (ultrastructure) Situs inversus (~50%)
CCDC114 ODA-defect Yes
ARMC4 ODA-defect Yes
CCDC151 ODA-defect Yes
TTC25 ODA-defect Yes

Assembly of ODA and IDA complexes

Name Phenotype (ultrastructure) Situs inversus (~50%)
LRRC50 (DNAAF1) ODA- and IDA-defect Yes
KTU (DNAAF2) Partial ODA- and IDA-defect Yes
DNAAF3 ODA- and IDA-defect Yes
DYX1C1 (DNAAF4) ODA- and IDA-defect Yes
LRRC6 ODA- and IDA-defect Yes
HEATR2 ODA- and partial IDA-defect Yes
ZMYND10 ODA- and IDA-defect Yes
SPAG1 ODA- and IDA-defect Yes
CFAP298 (C21orf59) ODA- and IDA-defect Yes
PIH1D3 ODA- and partial IDA-defect Yes
CFAP300 (C11orf70) ODA- and IDA-defect Yes

Component of the dynein regulatory complex (DRC)

Name Phenotype (ultrastructure) Situs inversus (~50%)
CCDC39 mislocalisation of the central pair; assembly of IDA and DRC is deficient yes
CCDC40 mislocalisation of the central pair; assembly of IDA and DRC is deficient yes
DRC1 (CCDC164) loss of the nexin bridges (difficult to detect) not documented
DRC4 (GAS8) deficient assembly of the nexin bridges not documented
DRC2 (CCDC65) reduction of the IDA complexes and the nexin bridges  

Component of the central sheat

Name Phenotype (ultrastructure) Situs inversus (~50%)
HYDIN loss of the "C2b"-structure (difficult to detect) No
STK36 normal ultrastructure No

Component of the radial spoke

Name Phenotype (ultrastructure) Situs inversus (~50%)
RSPH1 disturbed localisation of the central pair No
RSPH3 disturbed localisation of the central pair No
RSPH4A disturbed localisation of the central pair No
RSPH9 disturbed localisation of the central pair No
DNAJB13/RSPH16A disturbed localisation of the central pair No

Additional PCD-associated genes

Name Phenotype (ultrastructure) Situs inversus (~50%)
GAS2L2 defects in ciliary orientation ?
LRRC56 absence of ODA in distal portion of the axoneme Yes

An X-linked inheritance for PCD is associated with mutations in two other genes, RPGR and OFD1, and are associated with other serious disease manifestations.
Our group was significantly involved in the identification of 23 genes, whose mutations are associated with PCD. We are actively researching new causative genes for PCD.

From phenotype to candidate gene analysis
Primary ciliary dyskinesia is based on the failure of the structural and functional components of cilia and its associated proteins. At least 250 proteins are involved in the coordinated beating of cilia. Mutations in the genes corresponding to each of these 250 proteins could potentially lead to PCD. The genes are sometimes very large, such as axonemal dynein heavy chain 5 (DNAH5) of the outer dynein arm (ODA) component; DNAH5 alone has 80 coding segments (exons). A genetic analysis is therefore very expensive, especially since not all human genes for PCD have been identified yet.
In order to find new candidate genes, certain information is required. Linkage analysis (comparing the alleles of healthy and sick family members) provides information on the potential locus of the causative gene. The phenotype can provide clues regarding the function of the defective protein. For example, by high-speed video microscopy analysis, cilia that demonstrate a stiff, trembling beat pattern points to a defect in the inner dynein arms; an only occasional twitching or complete immotility of cilia, however, suggests a defect of the ODA. Immunofluorescence analysis (IF) provides more accurate information about the function and location of the desired gene product. Once a candidate gene is found, all coding gene segments are amplified by PCR and bidirectionally sequenced to identify potential mutations.

Autosomal recessive mode of inheritance: both parents have two copies (alleles) of each gene. If only one gene is altered by a mutation (marked with a slash), they themselves are healthy, but give this allele on to their children. The children receive one allele from each parent. With two mutant allels the child is ill.

Molecular genetic diagnosis

We, in collaboration with the Institute for Human Genetics at the University Hospital of Münster (Univ.-Prof. Dr. P. Wieacker), provide molecular genetic analysis of known genes in patients with PCD. The diagnosis of "PCD" is verified from our laboratory by immunofluorescence microscopy. Please think about the issue of a referral laboratory certificate.
Participation in our IF diagnosis is a prerequisite for the implementation of molecular genetic analysis. The consent of the patient includes the participation in our ongoing research. For further information and documentation, see the following links or contact directly our laboratory in Muenster.