NFE2L2 was first reported in relation to autosomal dominant immunodeficiency, developmental delay, and hypohomocysteinemia (IMDDHH) in 2017 (Huppke P et al., PMID:29018201). IMDDHH is a multisystem disorder characterized by immunodeficiency, mildly delayed psychomotor development, poor overall growth from infancy, and hypohomocysteinemia. Patients may also present with additional features such as congenital heart defects, potential liver damage, subcortical T2-weighted white matter abnormalities and other more variable phenotypes. At least 4 variants (all missense) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data.
In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.
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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