Expansion of the Mutation and Phenotype Spectrum of the GABRA2-related developmental and epileptic encephalopathy78

Background Developmental and epileptic encephalopathy 78 is a severe neurological disease characterized by intractable seizures and severe intellectual disability (ID). It was discovered in 2019 as a autosomal dominant genetic disease caused by heterozygous mutation in the GABRA2 gene(* 137140) which located on chromosome 4p12. So far,only 8 patients with 7 deleterious missense variants in the GABRA2 gene have been reported. Materials and methods In this study, Using Trio-Whole Exome Sequence, we discovered five novel GABRA2 variants in five unrelated patients belong to five different families. Furthermore, we systematically described all 13 patients’ clinical features and molecular genetics. Result Identified five novel deleterious variants in GABRA2 gene within five patients,one frameshift variant(c.988_c.989insTTATG, p.Glu330Valfs*22), four missense variants(c.644T > C, p.Leu215Ser; c.862A > G, p.Thr288Ala; c.166C > T, p.Arg56Trp; c.460C > G, p.Leu154Val). These patient cohort presents a complex array of neurological and developmental challenges, with a spectrum ranging from severe motor and cognitive impairment to varying degrees of seizure frequency and type, as well as resistance to pharmacological treatments. The variability in clinical presentation highlights the need for individualized approaches to treatment and care Conclusion In summary, Seizures were a phenotype observed in all patients, while there were other additional variable phenotypes. We identified five novel variants of the GABRA2 gene using Trio-whole exome sequence for the fist time in China, This study broadened the genetic and phenotypic spectrum of the GABRA2 gene