Table 1.

Molecular Genetics of Primary Ciliary Dyskinesia

Gene 1% of PCD
Caused by
Pathogenic
Variants
in Gene 2, 3		Distinguishing
Clinical Features		Findings
on Ciliary
Ultrastructure
Analysis		OMIM
Phenotype /
References
ODAD2
(ARMC4)		<3% 4Situs abnormalitiesODA defects 615451
CCDC39 4%-9%Situs abnormalities; worse lung function; ↑ bronchiectasis; poor weight gainIDA defects+MTD 613807
CCDC40 3%-4%Situs abnormalities; worse lung function; ↑ bronchiectasis; poor weight gainIDA defects+MTD 613808
CCDC65 5RareSitus abnormalities not reportedNormal ciliary ultrastructure 615504
CCDC103 <4% 4Situs abnormalitiesODA defects 614679
ODAD1 RareSitus abnormalitiesODA defects 615067
ODAD3
(CCDC151)		<3% 4Situs abnormalitiesODA defects 616037
CCNO RareSitus abnormalities not reportedOligocilia 6 615872
CFAP221 RareSitus abnormalities not reportedNormal ciliary ultrastructure Bustamante-Marin et al [2020]
CFAP298 RareSitus abnormalitiesODA+IDA defects 615500
CFAP300
(C11orf70)		RareSitus abnormalitiesODA+IDA defects618063 / Fassad et al [2018a], Höben et al [2018]
DNAAF1 RareSitus abnormalitiesODA+IDA defects 613193
DNAAF2 RareSitus abnormalitiesODA+IDA defects 612518
DNAAF3 RareSitus abnormalitiesODA+IDA defects 606763
DNAAF4 RareSitus abnormalitiesODA+IDA defects 615482
DNAAF5 RareSitus abnormalitiesODA+IDA defects 614874
DNAAF11
(LRRC6)		RareSitus abnormalitiesODA+IDA defects 614935
DNAH1 RareSitus abnormalitiesCiliary ultrastructure not defined 617577
DNAH5 15%-29%Situs abnormalitiesODA defects 608644
DNAH8 RareSitus status unknownCiliary ultrastructure not defined Watson et al [2014]
DNAH9 7RareSitus abnormalitiesSubtle ODA defects618300 / Fassad et al [2018b], Loges et al [2018]
DNAH11 86%-9%Situs abnormalitiesNormal ciliary ultrastructure 611884
DNAI1 2%-10%Situs abnormalitiesODA defects244400
DNAI2 RareSitus abnormalitiesODA defects 612444
DNAJB13 RareSitus abnormalities not reportedCP defects617091 / El Khouri et al [2016]
DNAL1 RareSitus abnormalitiesODA defects 614017
DRC1 5RareSitus abnormalities not reportedNormal ciliary ultrastructure 615294
FOXJ1 RareSitus abnormalities; AD MOINormal ciliary ultrastructure602291 / Wallmeier et al [2019]
GAS2L2 RareSitus abnormalities not reportedNormal ciliary ultrastructure 618449
GAS8 RareSitus abnormalities not reportedNormal ciliary ultrastructure.616726 / Olbrich et al [2015]
HYDIN 9RareSitus abnormalities not reportedNormal ciliary ultrastructure. 608647
LRRC56 10RareSitus abnormalitiesNormal ciliary ultrastructure 618254
MCIDAS RareSitus abnormalities not reportedOligocilia 6 Boon et al [2014]
NME8 RareSitus abnormalitiesODA defects (~66% of cross sections) 610852
OFD1 11RareSitus abnormalities; dysmorphic features; hypotonia; worse lung function; ↑ bronchiectasis; poor weight gain; XL MOINormal ciliary ultrastructure Hannah et al [2019]
PIH1D3 RareSitus abnormalities; XL MOIODA+IDA defects300991 / Olcese et al [2017], Paff et al [2017]
RSPH1 RareMilder lung disease; situs abnormalities not reportedCP defects 615481
RSPH3 RareSitus abnormalities not reportedCP defects 616481
RSPH4A RareSitus abnormalities not reportedCP defects 612649
RSPH9 RareSitus abnormalities not reportedCP defects 612650
SPAG1 <4% 4Situs abnormalitiesODA+IDA defects 615505
SPEF2 9RareSitus abnormalities not reported; can present w/isolated male infertilityNormal ciliary ultrastructure610172 / Cindrić et al [2020], Liu et al [2020], Liu et al [2019], Sha et al [2019]
STK36 RareSitus abnormalities not reportedCP defects607652 / Edelbusch et al [2017]
TTC25 RareSitus abnormalitiesODA defects617092 / Wallmeier et al [2016]
ZMYND10 <2%-4% 4Situs abnormalitiesODA+IDA defects 615444

AD = autosomal dominant;CP defects = central pair defects (note that most cilia may appear normal); IDA defects+MTD = inner dynein arm defects+microtubular disorganization; MOI = mode of inheritance; ODA defects = outer dynein arm defects; ODA+IDA defects = outer+inner dynein arms defects; XL = X-linked

1.

Genes are listed in alphabetical order.

2.

Rare = pathogenic variants in this gene reported in ≤2% of individuals with PCD

3.

Some estimates are extrapolations based on defects in ciliary structure (see Ciliary Ultrastructural Analysis).

4.

Gene was screened in a large cohort in a single study. Percentage may be an overestimate if the study cohort was selected on the basis of prior molecular genetic testing results (i.e., individuals with biallelic pathogenic variants in previously known genes were excluded).

5.

Encodes component of Nexin-Dynein regulatory complex

6.

Cilia biogenesis defect

7.

Encodes protein localized to the distal end of cilia

8.

Encodes outer dynein arm protein

9.

Encodes component of central pairs

10.

Encodes component of intraflagellar transport machinery

11.

OFD1 is implicated in classic oral-facial-digital syndrome type I, an X-linked disorder typically associated with male lethality, as well as additional phenotypes including Simpson-Golabi-Behmel syndrome type 2 (OMIM 300209). Hannah et al [2019] describe findings consistent with both PCD and Simpson-Golabi-Behmel syndrome in hemizygous males.

From: Primary Ciliary Dyskinesia

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