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Genetic assessment of GABBR2 in human brain development

Jeongha Lee¹, Murim Choi¹*

¹Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea

Rett syndrome (RTT) is a severe neurodevelopmental disorder that mostly affects girls as the main causal gene
MECP2 is located on X chromosome. We had previously elucidated the mechanism of pathogenic variants in GABBR2,

encodes a GABA B receptor, that also lead to RTT and epileptic encephalopathy (EE). While collecting GABBR2
patients that show variable brain features, we seek to establish a complete functional map of the gene. To do this,

we have been working on three different approaches. (1) Recruiting carriers of GABBR2 pathogenic variants, (2)
performing saturation mutagenesis by inducing all possible variations in GABBR2 and assessing their signaling

function in a quantitative manner, and (3) evaluating phenotypic effect of rare GABBR2 variants in the general
population (UK Biobank). Our approaches reveal genotype-phenotype relationships based on human patients and

healthy individuals, and high-throughput functional assay saturation mutagenesis.