左心室心肌致密化不全(LVNC)是一种罕见的先天性心脏病。在LVNC患者及其家庭成员中发现了基因缺陷;MYH7是与LVNC相关的最常见的基因。
我们对患有心脏异常的胎儿进行了完整的产前超声和超声心动图检查,并进行了亲子三人全外显子组测序,以确定潜在的遗传原因。当在胎儿中发现MYH7的遗传异常时,我们对其高危亲属进行了超声心动图和基因筛查.
孕中期超声和超声心动图显示胎儿有几种畸形:Ebstein异常(EA),心脏扩张,膜周部室间隔缺损,轻度腹膜,和单脐动脉.在该胎儿及其母亲中鉴定出剪接变体等位基因的杂合基因分型(NM_00025.3:c.732G>A),不是她父亲,表明是母本遗传。随后,直接测序证实了她的祖母(母亲的母亲)中存在这种剪接变体,母亲,姐姐,和她自己以杂合子的方式。对于从外周血细胞提取的RNA样品,通过qRT-PCR没有扩增PCR产物。除了这个先证者被诊断患有EA,她的姐姐和祖母(母亲的母亲)被诊断出患有孤立的无症状LVCN,但她的母亲只是一个携带者,在家庭筛查后没有明显的临床表现。
MYH7剪接变体c.732+G>A的存在可以是母系遗传的,和它的心脏表型是不同的从一个载体到另一个。
Left ventricular non-compaction cardiomyopathy (LVNC) is a rare congenital heart defect. Gene defections have been found in patients with LVNC and their family members; and MYH7 is the most frequent gene associated with LVNC.
We performed a complete prenatal ultrasound and echocardiographic examination on a fetus with cardiac abnormality and a parent-child trio whole-exome sequencing to identify the potential genetic causes. When the genetic abnormality in MYH7 was identified in the fetus, we performed echocardiography and genetic screening on its high-risk relatives.
Second trimester ultrasound and echocardiography showed several malformations in the fetus: Ebstein\'s anomaly (EA), heart dilatation, perimembranous ventricle septal defects, mild seroperitoneum, and single umbilical artery. Heterozygous genotyping of a splicing variant allele (NM_00025.3: c.732+G>A) was identified in this fetus and her mother, not her father, indicating a maternal inheritance. Subsequently, direct sequencing confirmed the presence of this splicing variant among her grandmother (mother of mother), mother, older sister, and herself in a heterozygous manner. No PCR products were amplified by qRT-PCR for the RNA samples extracted from peripheral blood cells. In addition to this proband who was diagnosed with EA, her older sister and grandmother (mother of mother) were diagnosed with isolated asymptomatic LVCN, but her mother was just a carrier with no marked clinical manifestations after family screening.
The presence of MYH7 splicing variant c.732+G>A can be inherited maternally, and its cardiac phenotypes are different from one carrier to another.