FIGURE 1.

Pathogenic variants in CFAP46 and CFAP54 cause primary ciliary dyskinesia with a defective C1d projection. a) Schematic of respiratory epithelium (left), an axonemal 9+2 cross-section (middle) and the ciliary central apparatus (CA) (right). CFAP46, CFAP54, CFAP74 and CFAP221 localise to the C1d projection of the CA. SPEF2 is part of the C1b projection, HYDIN of the C2b projection; STK36 is predicted to localise between the CA and radial spoke (RS). IDA: inner dynein arm; ODA: outer dynein arm; N-DRC: nexin-dynein regulatory complex. b) CFAP46 is located on chromosome 10 and encodes a 2715 amino acid (aa) protein with two coiled-coil motifs. The epitope of the anti-CFAP46 antibody is located between the two coiled-coil motifs and specifically recognises CFAP46. The positions of the identified pathogenic variants in CFAP46 are indicated by exons highlighted in red. Resulting truncated proteins are indicated below. c) CFAP54 is located on chromosome 12 and encodes a 3096 aa protein with a domain of unknown function (DUF) and a coiled-coil motif. The positions of the identified pathogenic variants in CFAP54 are indicated by exons highlighted in red. Resulting truncated proteins are indicated below.