FOXP2 was first reported in relation to autosomal dominant specific language disorder in 2001 (Lai et al., 11586359). At least 10 unique variants (missense, nonsense, frameshift and large deletions) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level and experimental data.
Summary of Case Level Data: Variants in this gene have been reported in at least 12 probands in 4 publications (11586359, 15877281, 23918746, 27572252), including a heterozygous de novo 14kb deletion of FOXP2 exons 12-17 (Reuter et al., 2016; 27572252) that would add an additional 2 points so the maximum score for genetic evidence (12 pts.) has been reached.
This gene-disease association is supported by animal models, expression studies and in vitro functional assays.
In summary, FOXP2 is definitively associated with autosomal dominant specific language 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 Working Group on 05/21/2019 (SOP Version 6)
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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