A family with Andersen-Tawil syndrome induced by a new mutation Q164R in the KCNJ2 gene and previous literature review / 中华神经科杂志

ABSTRACT

Objective To discuss clinical characteristics of a family with Andersen-Tawil syndrome, test and analyze the mutation of their pathogenic gene, and to discover the dependency of genotype and phenotype by searching every reported Andersen-Tawil syndrome patient in all accessible literature worldwide.Methods In December 2nd,2016,two patients in the Department of Neurology,the First Hospital of Shanxi Medical University, received medical history data collection and relevant examinations.PCR and DNA sequencing were applied to detect ion channel diseases related genes such as SCN4A, CACNA1S, KCNJ2, KCNE3, KCNE4, KCNJ18, KCNJ5.Random selection of 200 healthy volunteers from Shanxi Medical University served as normal controls.Andersen-Tawil syndrome cases,which are accorded with statistical criteria in published literature, were collected.Their genotype and phenotype were analyzed and summarized.Results Clinical manifestation of the pre-confirmed patient and his father was accorded with diagnostic criteria of Andersen-Tawil syndrome.Prominent characteristics included ventricular arrhythmia, periodic paralysis, and dysmorphic features.The two patients had renal tubular acidosis.One of these two patients also had increased level of renin-angiotensin-aldosterone.New mutation Q164R in the KCNJ2 gene was found in these two patients.There was no report in any literature or any database that we could find about this gene mutation at present.The mutation was not found among other healthy family members and 200 healthy controls.In this study,we referenced 55 samples of Andersen-Tawil syndrome in 12 articles,in which 54 samples are KCNJ2 gene mutation,one is KCNJ5 gene mutation.We concluded a negative correlation between the onset age of periodic paralysis and the onset age of cardiac symptoms after a statistical analysis of these 54 patients with KCNJ2 gene mutation(rs=-0.698 1,P=0.005 5).The incidence of cardiac symptoms in patients of Andersen-Tawil syndrome with periodic paralysis was reduced(33.33%(14/42)vs 9/11, χ2=6.485,P=0.011).Men(96.00%(24/25))were found more likely to have periodic paralysis than women(65.52%(19/29); χ2=7.691,P=0.006).Women (64.29%(18/28))were found more likely to have cardiac symptoms than men(20.00%(5/25); χ2=10.545,P=0.001).Conclusions New mutation Q164R in the KCNJ2 gene is the cause of Andersen-Tawil syndrome,which could cause renal tubular acidosis.We speculate that the gene may play a role in the way of potassium regulating aldosterone.For women with the KCNJ2 gene mutation and the late-onset of periodic paralysis,it is important to take drug or manual intervention as early as possible to prevent the occurrence of cardiogenic adverse events.