INTU was first reported in relation to autosomal recessive INTU-related skeletal ciliopathy in 2016 (Toriyama et al. 2016, PMID: 27158779). INTU-related skeletal ciliopathy is characterized by facial dysmorphism, tongue nodules, developmental delay, and polydactyly, as well as other syndromic findings. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability between orofaciodigital syndrome XVII (MIM: 617926) and short-rib thoracic dysplasia 20 with polydactyly (MIM: 617925). Therefore, the two disease assertions have been lumped into one entity, INTU-related skeletal ciliopathy.
A total of 2 missense, 2 frameshift, 1 nonsense, and 1 CNV that have been reported in four probands in three publications (PMIDs: 27158779, 29451301, 34623732) are included in this curation. The mechanism of pathogenicity at this time is unknown. This gene-disease relationship is also supported by two mouse models, rescue in non-human model organisms, biochemical function studies, and protein-protein interactions (PMIDs: 20067783, 22935613, 25774014, 27158779). In summary, there is definitive evidence supporting the relationship between INTU and autosomal recessive INTU-related skeletal ciliopathy. 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 Skeletal Disorders GCEP on the meeting date June 2nd, 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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