IFT74 was first reported in relation to autosomal recessive ciliopathy-IFT74 in 2016 (Lindstrand et al., PMID: 27486776). Variants in the IFT74 gene have been reported in individuals with a variety of ciliopathy phenotypes including Bardet-Biedl syndrome (BBS), Joubert syndrome (JBTS), Short rib polydactyly syndrome (SRPS), Jeune asphyxiating thoracic dystrophy (ATD), and primary ciliary dysplasia (PCD) in the literature. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, there were no differences in inheritance pattern, phenotypic variability, and molecular mechanism. Therefore, BBS, JBTS, SRPS, ATD, and PCD have been lumped into one disease entity. Of note, IFT74 has also been reported in a proband with isolated spermatogenic failure 58 (PMID: 33689014).
At least 11 unique variants (missense, nonsense, splicing, and deletion) that have been reported in 11 probands from 6 publications (PMIDs: 27486776, 33531668, 33748949, 34539760, 37315079, 37555648) are included in this curation. More information is available in the literature, but the maximum score for genetic evidence (12 pts) has been reached. This gene-disease relationship is also supported by functional studies showing ciliation defects in patient cells, and rescue in both zebrafish and mouse (PMIDs: 27486776, 33531668, 37315079). In summary, there is definitive evidence to support the relationship between IFT74 and autosomal recessive ciliopathy-IFT74. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy Disorders Gene Curation Expert Panel on August 27th, 2025 (SOP Version 11)
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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