We report on an 8-year-
old
girl with severe developmental and epileptic encephalopathy
due to the compound heterozygous null variants p.(Gln661*) and
p.(Leu830Profs*2) in GRIN2A resulting in a knockout of the human GluN2A subunit
of the N-methyl-
D-
aspartate
receptor. Both parents had less severe GRIN2A-related
phenotypes and were heterozygous carriers of the respective null variant.
Functional investigations of both variants suggested a loss-of-
function
effect. This
is the first description of an autosomal recessive, biallelic type of GRIN2A-related
disorder. Nonetheless, there are marked parallels to two previously published
families with severe epileptic encephalopathy due to homozygous null variants
in GRIN1 as well as various knockout animal models. Compared to heterozygous
null variants, biallelic knockout of either GluN1 or GluN2A is associated
with markedly more severe phenotypes in both humans and mice. Furthermore,
recent findings enable a potential precision medicine approach targeting GRIN-related
disorders due to null variants.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:91572 |
| Date | 22 May 2024 |
| Creators | Strehlow, Vincent, Rieubland, Claudine, Gallati, Sabina, Kim, Sukhan, Myers, Scott J., Peterson, Vincent, Ramsey, Amy J., Teuscher, Daniel D., Traynelis, Stephen F., Lemke, Johannes R. |
| Publisher | Wiley |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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