School of Public Health, Hubei University of Medicine, China.
Children's Medical Center, Taihe Hospital, Hubei University of Medicine, China.
Clinics (Sao Paulo). 2023 Sep 30;78:100285. doi: 10.1016/j.clinsp.2023.100285. eCollection 2023.
Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized.
Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation.
A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.
长 QT 综合征（LQTS）是一种遗传性疾病，心脏的电传导系统异常，可导致 QT 延长引起的猝死。LQTS 的第二大常见亚型是 LQT2，由钾电压门控通道亚家族 H 成员 2（KCNH2）基因突变导致功能丧失。尽管与 LQTS 相关的突变超过 900 种，但其中许多突变未经证实或特征不明。
对一个 LQT2 家族的基因组 DNA 进行测序分析，确定了一个假定的突变，即 KCNH2（NM_000238.3）：c.3099_3112del，该突变似乎是明确的致病突变。家族系谱信息显示，男女患者的临床特征和 T 波形态存在性别差异。携带突变的女性表现为反复发作的室性心律失常和晕厥，而两名男性携带者没有任何症状。此外，女性的 T 波比男性更平坦。女性先证者对利多卡因试验呈阳性反应。利多卡因注射几乎完全阻断了室性心律失常，并使 QT 间期缩短≥30ms。普罗帕酮、美西律治疗和植入心脏复律除颤器防止了持续性室性心动过速、心室颤动和晕厥，3 年随访评估结果显示。
KCNH2 基因中的假定突变 c.3099_3112del 导致 LQT2 综合征，致病性突变主要导致女性后代出现症状。
