CANT1 was first reported in relation to autosomal recessive Desbuquois dysplasia 1 in 2009 (Huber et al., PMID: 19853239). Desbuquois dysplasia is a rare type of osteochondrodysplasia characterized by short stature with short extremities, severe joint laxity with dislocation, and fetal growth restriction. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in inheritance pattern and phenotypic variability between Desbuquois dysplasia 1 and epiphyseal dysplasia, multiple, 7. Therefore, the disease entities have been lumped into one disease entity, Desbuquois dysplasia 1 (OMIM:251450). 7 frameshift, 6 missense, and 2 nonsense variants that have been reported in 13 probands in 6 publications (PMIDs: 19853239, 22539336, 25252066, 28229453, 28742282, 31988067) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is currently unknown. This gene-disease relationship is also supported by functional alteration of patient cells and animal models (PMIDs: 19853239, 30439444, 32277574). In summary, there is definitive evidence supporting the relationship between CANT1 and autosomal recessive Desbuquois dysplasia 1. 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 Prenatal GCEP on the meeting date September 10th, 2024 (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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