EXOC7 was first reported in relation to autosomal recessive neurodevelopmental disorder with seizures and brain atrophy in 2020 (Coulter et al., 2020, PMID: 32103185). Partial loss-of-function variants in EXOC7 are associated with developmental brain disorders of variable severity characterized by developmental delay, seizures, brain atrophy, microcephaly, and infantile death. Given the spectrum of neurodevelopmental features observed, the gene is curated under “complex neurodevelopmental disorder” (http://purl.obolibrary.org/obo/MONDO_0100038).
Four variants (1 splice site mutation, 2 in-frame deletions, and 1 missense mutation) reported in four probands in one publication are included in this curation. All variants are predicted to yield hypomorphic alleles. This gene-disease relationship is also supported by a zebrafish animal model (Coulter et al., 2020, PMID: 32103185).
In summary, there is moderate evidence supporting the relationship between EXCO7 and AR neurodevelopmental disorder with seizures and brain atrophy. This has not been repeatedly demonstrated in both the research and clinical diagnostic settings. This classification was approved by the Intellectual Disability and Autism Gene Curation Expert Panel on the meeting date June 20, 2023 (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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