PRDM16 (positive regulatory domain 16) is localized in the critical region for cardiomyopathy in patients with deletions of chromosome 1p36, as defined by Gajecka et al., American Journal of Medical Genetics, 2010, 152A, 3074-3083, and encodes a zinc finger transcription factor. We present the first fetal case of left ventricular non-compaction (LVNC) with a PRDM16 variant. The third-trimester obstetric ultrasound revealed a hydropic fetus with hydramnios and expanded hypokinetic heart. After termination of pregnancy, foetopathology showed a eutrophic fetus with isolated cardiomegaly. Endocardial fibroelastosis was associated with non-compaction of the myocardium of the left ventricle. Exome sequencing (ES) identified a de novo unreported p.(Gln353*) heterozygous nonsense variant in PRDM16. ES also identified two rare variants of unknown significance, according to the American College of Medical Genetics and Genomics guidelines, in the titin gene (TTN): a de novo missense p.(Lys14773Asn) variant and a c.33043+5A>G variant inherited from the mother. Along with the PRDM16 de novo probably pathogenic variant, TTN VOUS variants could possibly contribute to the severity and early onset of the cardiac phenotype. Because of the genetic heterogeneity of cardiomyopathies, large panels or even ES could be considered as the main approaches for the molecular diagnosis, particularly in fetal presentations, where multiple hits seem to be common.

中文翻译：

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PRDM16突变引起的心肌病：胎儿表现的首次描述，可能带有修饰基因。

如Gajecka等人在《美国医学遗传学杂志》（American Journal of Medical Genetics），2010，152A，3074-3083所定义，PRDM16（正调控域16）位于1p36染色体缺失患者的心肌病关键区域，并编码锌指转录因子。我们介绍了第一例PRDM16变异的左心室非致密性胎儿（LVNC）。妊娠晚期的产科超声检查发现有水肿的胎儿羊水过多，心脏运动功能减退。妊娠终止后，胎儿病理学检查显示胎儿富营养化并伴有孤立的心脏肥大。心内膜纤维弹性增生与左心室心肌不紧密相关。外显子组测序（ES）在PRDM16中鉴定出从未报道过的p。（Gln353 *）杂合无义变体。根据美国医学遗传学和基因组学指南，ES还发现了titin基因（TTN）中两个未知重要性不高的稀有变体：一种新的错义p。（Lys14773Asn）变体和一个c.33043 + 5A> G变体。从母亲那里继承来的。TTN VOUS变异可能与PRDM16 de novo可能的致病变异一起，可能会影响心脏表型的严重性和早期发作。由于心肌病的遗传异质性，大样本甚至是ES可以被认为是分子诊断的主要方法，尤其是在胎儿表现形式中，这种表现似乎很常见。G变体继承自母亲。TTN VOUS变异可能与PRDM16 de novo可能的致病变异一起，可能会影响心脏表型的严重性和早期发作。由于心肌病的遗传异质性，大样本甚至是ES可以被认为是分子诊断的主要方法，尤其是在胎儿表现形式中，这种表现似乎很常见。G变种从母亲那里继承而来。TTN VOUS变异可能与PRDM16 de novo可能的致病变异一起，可能会影响心脏表型的严重性和早期发作。由于心肌病的遗传异质性，大样本甚至是ES可以被认为是分子诊断的主要方法，尤其是在胎儿表现形式中，这种表现似乎很常见。