NFIA was first reported in relation to autosomal dominant brain malformations with or without urinary tract defects in 2007 (Lu et al., PMID: 17530927). Most individuals present with some combination of agenesis of the corpus callosum, ventriculomegaly, developmental delay, intellectual disability, and/or urinary tract defects. Seven variants (nonsense, frameshift, large deletion etc) that have been reported in seven probands in six publications (PMIDs: 22542183, 24462883, 27081522, 28941020, 32926563, 35080095) are included in this curation. The variants reported in this curation arose de novo as did most observed variants throughout the literature. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be LOF. This gene-disease association is also supported by demonstrated biochemical function, expression in relevant tissues, and a knockout mouse model (PMIDs: 10718198, 17530927, 26512640, 29247144). In summary, NFIA is definitively associated with autosomal dominant brain malformations with or without urinary tract defects. 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 Brain Malformations Gene Curation Expert Panel on 10/11/2022 (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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