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Long QT syndrome (LQTS) is a rare inherited arrhythmia marked by prolonged cardiac repolarization and risk of syncope, ventricular fibrillation, and sudden cardiac death. The RNF207 gene encodes a ring finger protein implicated in potassium channel regulation and is emerging as a candidate in LQTS pathogenesis alongside established ion‐channel genes.
In a Chinese family with Long QT syndrome and syncope, whole‐exome sequencing identified a novel nonsense variant, c.439C>T (p.Gln147Ter), in the RNF207 gene that co‐segregated with disease in 1 proband ([PMID:30542207]) and 2 affected relatives ([PMID:30542207]). Real‐time PCR demonstrated marked RNF207 mRNA reduction consistent with nonsense-mediated decay, supporting a haploinsufficiency mechanism and potential downstream impairment of KCNH2 channel activation. This single‐family report provides limited but compelling evidence for RNF207 deficiency in autosomal dominant LQTS.
Gene–Disease AssociationLimitedSingle Chinese family with a novel RNF207 loss-of-function variant co-segregating with disease and no additional unrelated cases. Genetic EvidenceLimitedOne proband and two affected relatives with a truncating RNF207 variant; no further unrelated cases reported. Functional EvidenceModerateReal-time PCR showed significant RNF207 mRNA reduction consistent with nonsense-mediated decay, supporting haploinsufficiency impacting KCNH2 channel function. |