TABLE 2.
MUTATIONS IN THE GENES THAT CAUSE HUMAN PRIMARY CILIARY DYSKINESIA
| Human Gene | Human Chromosomal Location | Chlamydomonas Ortholog | Ciliary Ultrastructure in Subjects with Biallelic Mutations | Presence of Laterality Defects | % of Individual with Biallelic Mutations | MIM No. | References |
|---|---|---|---|---|---|---|---|
|
DNAH5 |
5p15.2 |
DHC ɣ |
ODA defect |
Yes |
15–21% of all PCD, 27–38% of PCD with ODA defects |
608644 |
2, 16 |
|
DNAI1 |
9p21-p13 |
IC78 |
ODA defect |
Yes |
2–9% of all PCD, 4–13% of PCD with ODA defects |
244400 |
2, 16 |
|
DNAI2 |
17q25 |
IC69 |
ODA defect |
Yes |
2% of all PCD, 4% of PCD with ODA defects |
612444 |
16 |
|
DNAL1 |
14q24.3 |
LC1 |
ODA defect |
Yes |
na |
614017 |
16, 81 |
|
CCDC114 |
19q13.32 |
DC2 |
ODA defect |
Yes |
6% of PCD with ODA defects |
615038 |
83, 84 |
|
TXNDC3 (NME8) |
7p14-p13 |
LC5 |
Partial ODA defect (66% cilia defective) |
Yes |
na |
610852 |
16 |
|
DNAAF1 (LRRC50) |
16q24.1 |
ODA7 |
ODA + IDA defect |
Yes |
17% of PCD with ODA + IDA defects |
613193 |
16 |
|
DNAAF2 (KTU) |
14q21.3 |
PF13 |
ODA + IDA defect |
Yes |
12% of PCD with ODA + IDA defects |
612517, 612518 |
16 |
|
DNAAF3 (C19ORF51) |
19q13.42 |
PF22 |
ODA + IDA defect |
Yes |
na |
606763 |
75 |
|
CCDC103 |
17q21.31 |
PR46b |
ODA + IDA defect |
Yes |
na |
614679 |
77 |
|
HEATR2 |
7p22.3 |
Chlre4 gene model 525994 Phytozyme v8.0 gene ID Cre09.g39500.t1 |
ODA + IDA defect |
Yes |
na |
614864 |
79 |
|
LRRC6 |
8q24 |
MOT47 |
ODA + IDA defect |
Yes |
11% of PCD with ODA + IDA defects |
614930 |
80 |
|
CCDC39 |
3q26.33 |
FAP59 |
IDA defect + axonemal disorganization |
Yes |
36–65% of PCD with IDA defects + Axonemal disorganization |
613798 |
16, 82 |
|
CCDC40 |
17q25.3 |
FAP172 |
IDA defect + axonemal disorganization |
Yes |
24–54% of PCD with IDA defects + Axonemal disorganization |
613808 |
16, 82 |
|
RSPH4A |
6q22.1 |
RSP4, RSP6 |
Mostly normal, CA defects in small proportion of cilia |
No |
na |
612649 |
16 |
|
RSPH9 |
6p21.1 |
RSP9 |
Mostly normal, CA defects in small proportion of cilia |
No |
na |
612648 |
16 |
|
HYDIN |
16q22.2 |
hydin |
Normal, very occasionally CA defects |
No |
na |
610812 |
76 |
|
DNAH11 |
7p21 |
DHC β |
Normal |
Yes |
6% of all PCD, 22% of PCD with normal ultrastructure |
603339 |
16 |
|
RPGR |
Xp21.1 |
na |
Mixed |
No |
PCD cosegregates with X-linked Retinitis Pigmentosa |
300170 |
16 |
|
OFD1 |
Xq22 |
OFD1 |
nd |
No |
PCD cosegregates with X-linked mental retardation |
312610 |
16 |
| CCDC164 (C2ORF39) | 2p23.3 | DRC1 | Nexin (N-DRC) link missing; axonemal disorganization in small proportion of cilia | No | na | 312610 | 85 |
Definition of abbreviations: CA = central apparatus; IDA = inner dynein arm; MIM = Mendelian inheritance in man; na = not available; N-DRC = nexin–dynein regulatory complex; ODA = outer dynein arm; PCD = primary ciliary dyskinesia.
MIM number is the online MIM (www.ncbi.nlm.nih.gov/omim), which is a continuously updated catalog of human genes, genetic disorders, and traits, with particular focus on the molecular relationship between genetic variation and phenotype expression.