SATB1 was first reported in relation to autosomal dominant complex neurodevelopmental disorder in 2021 in a case study of 42 individuals (den Hoed et al., PMID: 33513338). Individuals with missense mutations in one of the DNA-binding domains (CUT1 and CUT2) were characterized by global developmental delay, moderate to severe intellectual disability, dysmorphic features, teeth abnormalities, autistic features, and early-onset epilepsy. Those with nonsense or frameshift mutations were characterized by mild global developmental delay with variably impaired intellectual development and autistic behaviors (PMIDs: 33513338, 34615535). Given the spectrum of neurodevelopmental features observed, the gene is curated for autosomal dominant complex neurodevelopmental disorder.
Twenty-five variants (missense, nonsense, frameshift, and splice variant) that have been reported in 34 probands in 2 publications (PMIDs: 33513338, 34615535) are included in this curation. Both females and males were equally affected and most reported variants were de novo. Recurrence of a few missense variants was observed in non-related individuals. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached.
In summary, there is definitive evidence supporting the relationship between SATB1 and autosomal dominant complex neurodevelopmental disorder. This has been repeatedly demonstrated in both 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 September 17th 2024 (SOP Version 10).
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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