Key result
Co-expression of P535T and A300T KCNQ1 mutations resulted in decreased plasma membrane colocalization, slow activation rise-time, and a use-dependent response, compatible with recessive Romano-Ward syndrome.
Why the study?
Functional studies of mutants are needed to establish variant pathogenicity and understand the mechanistic basis of disease for two compound heterozygous KCNQ1 mutations (p.A300T and p.P535T) identified in a child with sudden death.
Functional characterization of P535T/A300T KCNQ1 mutations reveals biophysical properties compatible with recessive Romano-Ward syndrome, providing mechanistic insight into their pathogenicity.
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Functional data on KCNQ1 variants may aid pathogenicity assessment; leaves open validation in larger recessive LQT1 cohorts.
González-Garrido et al. (2021) studied Recessive Romano-Ward Syndrome (Long QT Syndrome). KCNQ1 A300T and P535T mutant co-expression vs. Wildtype KCNQ1 was evaluated on Channel biophysical properties (activation V1/2, maximum conductance density, rise-time, and plasma membrane colocalization). Co-expression of P535T and A300T KCNQ1 mutations resulted in decreased plasma membrane colocalization, slow activation rise-time, and a use-dependent response, compatible with recessive Romano-Ward syndrome.
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