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 (NM_002232.4) variant (c.1433T>A, p.Val478Glu) and an inherited KCNQ3 (NM_004519.3) 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, E., Colona, V.l., Agolini, E., Murdocca, M., Russo, M., Stellato, M., et al. (2026). A de novo KCNA3 and an inherited KCNQ3 missense variant causing a developmental and epileptic encephalopathy, intellectual disability, and behavioral anomalies. NEUROGENETICS, 27(1), 1-9 [10.1007/s10048-026-00879-2].
A de novo KCNA3 and an inherited KCNQ3 missense variant causing a developmental and epileptic encephalopathy, intellectual disability, and behavioral anomalies
Marchionni, E.;Colona, V. L.;Murdocca, M.;Stellato, M.;Campione, E.;Spitalieri, P.;Mazzone, L.;Sangiuolo, F.;Novelli, G.
2026-01-01
Abstract
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 (NM_002232.4) variant (c.1433T>A, p.Val478Glu) and an inherited KCNQ3 (NM_004519.3) 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 strategyI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
