| http://purl.uniprot.org/citations/24140113 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24140113 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24140113 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2013.09.012"xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2013.09.012"xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Brown M.A."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Brown M.A."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Duncan E.L."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Duncan E.L."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Li C."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Li C."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Leo P.J."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Leo P.J."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Jones S.J."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Jones S.J."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "McInerney-Leo A.M."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "McInerney-Leo A.M."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Mitchison H.M."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Mitchison H.M."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Kayserili H."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Kayserili H."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Hartley J.L."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Hartley J.L."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Hildebrandt F."xsd:string |
| http://purl.uniprot.org/citations/24140113 | http://purl.uniprot.org/core/author | "Hildebrandt F."xsd:string |