TRIP12 was first reported in relation to autosomal dominant complex neurodevelopmental disorder in 2008 (Doco-Fenzy et al., PMID: 18822396). Individuals with variants in this gene have been reported to have delayed psychomotor development with delayed walking, mildly impaired intellectual development, learning difficulties, autistic features, or behavioral abnormalities. Most had fluent speech, although several patients had delayed speech. Additional features included hypotonia (4 patients), seizures (3 patients), and strabismus (2 patients). Given the spectrum of neurodevelopmental features observed, this gene was curated for the disease entity "complex neurodevelopmental disorder".
Twenty-seven variants (missense, in-frame indel, nonsense, frameshift, large deletions, etc.) have been reported in 25 probands in 6 publications (PMIDs: 25418537, 27848077, 18822396, 27479843, 28251352, 32424948) and 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 presumed mechanism of pathogenicity based on published evidence is loss of function.
In summary, TRIP12 is definitively associated with autosomal dominant complex neurodevelopmental disorder. 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 Intellectual Disability and Autism Expert Panel on April 5th, 2022 (SOP Version 9).
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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