云南玉溪市一家族性肥厚型心肌病家系致病基因筛查
Genetic Screening of Familial Hypertrophic Cardiomyopathy in Yuxi Yunnan
-
摘要: 目的 对云南省玉溪市一个家族性肥厚型心肌病的家系成员进行候选致病基因筛查, 分析基因型和表型之间的关系, 为家族性肥厚型心肌病的分子遗传学机制研究、早期筛查、早期干预治疗提供重要的理论基础.方法 对家系成员进行详细的病史采集、体格检查、常规十二导联心电图、心脏彩超检查;采集外周静脉血样本进行基因学检测.绘制家系遗传图谱, 分析家系遗传特点、基因型及临床表型.结果 该家系肥厚型心肌病的遗传方式以X连锁显性遗传为主.候选基因筛查发现家系中携带GLA、ZFPM2、SCN5A基因的错义突变, 且翻译的氨基酸发生改变.结论 X连锁显性遗传是该家系HCM主要的遗传方式.GLA c.167G>A (p.Cys56Tyr) 杂合或半合子错义突变可能是该家系肥厚型非梗阻性心肌病的主要致病突变.ZFPM2 c.1332G>C (p.Lys444Asn) 杂合错义突变和SCN5A c.5216G>A (p.Arg1739Gln) 杂合错义突变在该家系中临床意义未明.Abstract: Objective Through the screening of candidate pathogenic gene among family members of a family with familial hypertrophic cardiomyopathy in Yuxi, Yunnan Province, the study is designed to analyze the relationship between genotype and phenotype and to provide an important theoretical basis for the research of molecular genetic mechanism, early screening and early intervention of familial hypertrophic cardiomyopathy.Me thods A detailed medical history was collected and physical examination and routine twelve lead electrocardiogram and cardiac ultrasonography examination were performed among the family members. The peripheral venous blood samples were collected for genetic testing. The genetic map was drawn and the genetic characteristics, genotype and clinical phenotype were analyzed. Re s ults In this family, the dominant inheritance mode of hypertrophic cardiomyopathy is X-linked dominant inheritance. Candidate genes screening showed that a missense mutation was found in the GLA, ZFPM2, SCN5 A genes and the translated amino acids were changed.Conclus ion X-linked dominant inheritance is the main genetic mode of HCM in this family. GLA c.167 G> A (p.Cys56 Tyr) heterozygous or hemizygous missense mutation may be the major pathogenic mutation in this family with non-obstructive hypertrophic cardiomyopathy. The clinical significance of ZFPM2 c.1332 G> C (p.Lys444 Asn) heterozygous missense mutation and SCN5 A c.5216 G> A (p.Arg1739 Gln) heterozygous missense mutation in this family is undetermined.
-
Key words:
- Hypertrophic cardiomyopathy /
- Gene mutation /
- Phenotype
-
[1] [1]CHAUVEAU C, ROWELL J, FERREIRO A.A rising titan:TTN review and mutation update[J].Human Mutation, 2014, 35 (9) :1046. [2] [2]MARON B J, OMMEN S R, SEMSARIAN C, et al.Hypertrophic cardiomyopathy:present and future, with translation into contemporary cardiovascular medicine.[J].Journal of the American College of Cardiology, 2014, 64 (1) :83-99. [3] [3]GARMAN S C, GARBOCZI D N.The Molecular defect leading to fabry disease:Structure of humanα-galactosidase[J].Journal of Molecular Biology, 2004, 337 (2) :319. [4] [4]AL-THIHLI K, EBRAHIM H, HUGHES D A, et al.A variant of unknown significance in the GLA, gene causing diagnostic uncertainty in a young female with isolated hypertrophic cardiomyopathy[J].Gene, 2012, 497 (2) :320-322. [5] [5]STEPHAN F, HABER R.Fabry disease[J].Heart, 2017, 89 (8) :819-820. [6]赵新涛, 陈伊, 冯新星, 等.Fabry病在中国汉族肥厚型心肌病人群的患病率 (英文) [J].现代生物医学进展, 2014, 14 (11) :2006-2010. [7] [6]SHENG W, CHEN L, WANG H, et al.Cp G island shore methylation of ZFPM2 is identified in tetralogy of Fallot samples[J].Pediatr Res, 2016, 80 (1) :151-158 [8] [8]SURHONE L M, TENNOE M T, HENSSONOW S F, et al.ZFPM2[M].Betascript Publishing, 2011:16-40. [9]盛伟.法洛四联症患者心肌组织基因甲基化变异及机制研究[D].上海:复旦大学, 2012. [10]张鑫, 蒋立虹, 侯宗柳.先天性心脏畸形相关基因研究时展[J].昆明医科大学学报, 2009, 30 (S2) :55-58. [11] [11]TSANG S Y, MEI L, WAN W, et al.Glioma Association and Balancing Selection of ZFPM2[J].Plos One, 2015, 10 (7) :e0133003. [12]高元丰, 刘文玲, 胡大一, 等.钠通道相关遗传性心律失常的SCN5A基因筛查[J].中国心脏起搏与心电生理杂志, 2013, 26 (2) :107-110. [13] [13]ALPERT N R, MOHIDDIN S A, TRIPODI D, et al.Molecular and phenotypic effects of heterozygous, homozygous, and compound heterozygote myosin heavy-chain mutations[J].Am J Physiol Heart Circ Physiol, 2005, 288 (3) :H1097-102. [14] [14]MARON B J, MARON M S, SEMSARIAN C.Double or compound sarcomere mutations in hypertrophic cardiomyopathy:A potential link to sudden death in the absence of conventional risk factors[J].Heart Rhythm, 2012, 9 (1) :57-63. -
点击查看大图
计量
- 文章访问数: 2303
- HTML全文浏览量: 788
- PDF下载量: 49
- 被引次数: 0
下载:
