A de novo KCNA3 variant and an inherited KCNQ3 variant in a patient with DEE resulted in significantly decreased transcript and protein levels, supporting the rationale for channel-targeted treatment strategies.
De novo KCNA3 variants cause a Developmental and Epileptic Encephalopathy (DEE). We describe a 14-year-old boy presenting with DEE and carrying a heterozygous de novo KCNA3 (NM₀02232. 4) variant (c. 1433T>A, p. Val478Glu) and an inherited KCNQ3 (NM₀04519. 3) variant (c. 1720C>T, p. Pro574Ser). Human dermal fibroblasts (HDFs) were isolated from the patient and an age-matched control. KCNA3 and KCNQ3 transcript levels were quantified by qRT-PCR, showing in patient-HDFs a reduction of 77% and 40%, respectively (p < 0. 0001; p = 0. 0002). Western blot confirmed decreased KCNA3 and KCNQ3 protein levels by 50% and 35%, respectively (p < 0. 05). The contributing role of both variants supports the rationale for a channel-targeted treatment strategy.
Marchionni et al. (Fri,) studied this question.