复发性扩张型心肌病的罕见临床表现及MYNPC3、KCNH2和线粒体半胱氨酸tRNA序列变异的鉴定

Guillen Sacoto Maria J, Chapman Kimberly A, Heath Deneen, Seprish Mary Beth, Zand Dina J

Medical Genetics Training Program, National Human Genome Research Institute, National Institutes of Health, 35 Convent Drive, MSC 3717 Room 1B207, Bethesda, MD 20892-3717, USA.

Division of Genetics and Metabolism, Children's National Medical Center, 111 Michigan Avenue, N.W., Washington D.C. 20010, USA.

Mol Genet Metab Rep. 2015 Apr 13;3:47-54. doi: 10.1016/j.ymgmr.2015.03.007. eCollection 2015 Jun.

We describe a young girl with dilated cardiomyopathy, long QT syndrome, and possible energy deficiency. Two major sequence changes were identified by whole exome sequencing (WES) and mitochondrial DNA analysis that were interpreted as potentially causative. Changes were identified in the KCNH2 gene and mitochondrial tRNA for cysteine. A variation was also seen in MYPBC3. Since the launch of WES as a clinically available technology in 2010, there has been concern regarding the identification of variants unrelated to the patient's phenotype. However, in cases where targeted sequencing fails to explain the clinical presentation, the underlying etiology could be more complex than anticipated. In this situation, the extensive reach of this tool helped explain both her phenotype and family history.

我们描述了一名患有扩张型心肌病、长QT综合征且可能存在能量缺乏的年轻女孩。通过全外显子组测序（WES）和线粒体DNA分析确定了两个主要的序列变化，这些变化被认为具有潜在致病性。在KCNH2基因和线粒体半胱氨酸转运RNA中发现了变化。在MYPBC3中也发现了一个变异。自2010年WES作为一种临床可用技术推出以来，人们一直担心识别出与患者表型无关的变异。然而，在靶向测序无法解释临床表现的情况下，潜在病因可能比预期的更复杂。在这种情况下，该工具的广泛覆盖范围有助于解释她的表型和家族史。