Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, 
subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. 
All six IFT-A components and their motor protein, DYNC2H1, have been linked to 
human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; 
also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino 
syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the 
exception of IFT80, have unknown roles in human disease. To identify additional 
IFT-B components defective in ciliopathies, we independently performed different 
mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 
1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome 
resequencing in 63 individuals with ATD. We thereby detected biallelic mutations 
in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals 
displayed abnormalities of the thorax and/or long bones, as well as renal, 
hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. 
Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert 
syndrome was present in 2 out of 12 families. Fibroblasts from affected 
individuals showed disturbed ciliary composition, suggesting alteration of 
ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated 
the human phenotype and demonstrated a genetic interaction between ift172 and 
ift80. In summary, we have identified defects in IFT172 as a cause of complex 
ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an 
additional IFT-B component, IFT172, similar to what has been shown for IFT-A.