Objectives Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterised by an increase heart rate, syncope and an elevated plasma norepinephrine in response to posture change. None of mutations were directly associated with POTS, although some variations have been identified in the norepinephrine transporter gene. Mutations in any gene related to autonomic nervous system and cardiovascular system could promote the development of POTS, even be the pathogenic gene.

Methods We studied twentyfour probands suspected of suffering from channelopathy enrolled in the National Channellopathy Registry Study. The clinical characteristic was investigated, including family and personal medical histories, 12-lead electrocardiography and 24-hour ambulatory electrocardiography. DNA samples of the probands and their parents were extracted from serum leukocyte. LQTS1-3 genes and 45 exons of RYR2 gene where the known mutation clusters located were first identified by direct DNA-sequencing. Mutation analysis for the probands’ families would proceed if the results of proband were positive.

Results LTQS13 genes tests were negative and a heterozygous mutation (c.5428G>C) in RyR2 gene was identified to cause acid amino missense mutation (p. V1810L) and absent in 200 reference alleles. The mutated residues exhibit high conservation across species. p. V1810L was found a paternally inherited missense mutation. The proband was a twelve-year old girl. She has experienced recurrent episode of syncope at the time of her position change since she was nine years old. The electrocardiogram documented a prolonged QT interval of 548ms when she was in standing position and a diagnosis of Long QT syndrome (LQTS) was assumed. However, the QT interval was not prolonged in supine position and a heart rate increase at least 35bpm was documented in a upright test, which were not the typical features of LQTS. RyR2 gene was known as a susceptibility gene of catecholaminergic polymorphic ventricular tachycardia (CPVT)

Conclusions The symptom of orthostatic tachycardia indicates a diagnosis of POTS. LQTS, CPVT and POTS are different disease, but all of them are associated with increased sympathetic activation. Because ion channel has a pivotal role in cardiac systole, we hypothesise that RyR2 gene mutation could cause a clinic manifestation of POTS, even be another POTS-associated gene. Although no study has reported that RyR2 gene is associated with POTS, our finding provides new insights into the mechanism of POTS.