Sun Qiqing, Guo Jun, Hao Chanjuan, Guo Ruolan, Hu Xuyun, Chen Yuanying, Yang Weili, Li Wei, Feng Yingjun
Department of Cardiology Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital Zhengzhou China.
Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children; Genetics and Birth Defects Control Center, Beijing Children's Hospital Capital Medical University, National Center for Children's Health Beijing China.
Pediatr Investig. 2020 Mar 17;4(1):11-16. doi: 10.1002/ped4.12183. eCollection 2020 Mar.
Pathogenic variants in the gene are associated with aggressive dilated cardiomyopathy (DCM). Recently, was found to be associated with left ventricular non-compaction cardiomyopathy (LVNC). Thus far, only five families with LVNC have been reported to carry variants in . It remains unknown whether the variants in associated with DCM can also cause LVNC.
To elucidate the causative variant in two unrelated patients with both LVNC and DCM, and to identify the clinical characteristics associated with variants in .
Trio whole-exome sequencing (WES) was performed. Variants were filtered and classified in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG).
We identified two distinct variants in (one per patient) in these two patients with LVNC. Both variants have been reported in patients with DCM, without the LVNC phenotype. Patient 1 was an 11-year-old girl who had DCM, LVNC, and heart failure; the ratio of noncompacted-to-compacted myocardium was 2.7:1. A heterozygous variant c.1907G>A (p.Arg636His) in exon 9 was identified in this patient. Patient 2 was a 13-year-old boy who had clinical phenotypes identical to those of Patient 1; the ratio of noncompacted-to-compacted myocardium was 3.2:1 in this patient. WES revealed a heterozygous variant c.1909A>G (p.Ser637Gly) in exon 9. Both variants were previously characterized as pathogenic, and our study classified them as pathogenic variants based on the ACMG guidelines.
We found that two patients with LVNC had variants in . Our results extended the clinical spectrum of the two variants and illustrated that the same variant in can cause DCM, with or without the LVNC phenotype.
该基因中的致病变异与侵袭性扩张型心肌病（DCM）相关。最近，发现其与左心室心肌致密化不全心肌病（LVNC）有关。迄今为止，仅有五个患有LVNC的家系被报道携带该基因的变异。与DCM相关的该基因变异是否也能导致LVNC仍不清楚。
阐明两名患有LVNC和DCM的非亲缘关系患者中的致病基因变异，并确定与该基因变异相关的临床特征。
进行三联体全外显子组测序（WES）。根据美国医学遗传学与基因组学学会（ACMG）的指南对变异进行筛选和分类。
在这两名患有LVNC的患者中，我们在该基因中鉴定出两个不同的变异（每位患者一个）。这两个变异在患有DCM但无LVNC表型的患者中均有报道。患者1是一名11岁女孩，患有DCM、LVNC和心力衰竭；非致密心肌与致密心肌的比例为2.7:1。在该患者中鉴定出第9外显子的一个杂合变异c.1907G>A（p.Arg636His）。患者2是一名13岁男孩，其临床表型与患者1相同；该患者非致密心肌与致密心肌的比例为3.2:1。WES显示第9外显子有一个杂合变异c.1909A>G（p.Ser637Gly）。这两个变异先前均被鉴定为致病变异，我们的研究根据ACMG指南将它们分类为致病变异。
我们发现两名患有LVNC的患者该基因存在变异。我们的结果扩展了这两个基因变异的临床谱，并表明该基因中的相同变异可导致有或无LVNC表型的DCM。
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