Autosomal dominant hypertension with brachydactyly type E syndrome caused by pathogenic variants in the PDE3A gene was first reported in 2015. To date, there are only a few reports of this kind of syndrome. Other patients still lack a genetic diagnosis. Whole-exome sequencing was performed in an 18-year-old female proband with a clinical diagnosis of hypertension with brachydactyly syndrome. Quantitative real-time PCR was used to identify pathogenic copy number variations (CNVs). After bioinformatics analysis and healthy control database filtering, we revealed a heterozygous missense PDE3A variant (c.1346G > A, p.Gly449Asp). The variant was absent in the ExAC database and located in a highly evolutionarily conserved cluster of reported PDE3A pathogenic variants. Importantly, this variant was predicted to affect protein function by both SIFT (score = 0) and PolyPhen-2 (score = 1). After Sanger sequencing, the variant was determined to be absent in the healthy parents of the proband as well as 800 ethnically and geographically matched healthy controls. We present a report linking a de novo PDE3A variant to autosomal dominant hypertension with brachydactyly type E syndrome.

中文翻译：

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全外显子组测序鉴定了从头PDE3A变异体，该变异体导致常染色体显性高血压并伴有近距离E型综合征：一例病例报告。

由PDE3A基因的致病性变异引起的常染色体显性遗传性高血压伴E型近距离假性综合征首次报道于2015年。迄今为止，此类综合征的报道很少。其他患者仍缺乏遗传诊断。全外显子组测序是在18岁的女性先证者中进行的，该先证者临床诊断为患有近距离接触综合征的高血压。实时定量PCR用于鉴定致病性拷贝数变异（CNV）。经过生物信息学分析和健康对照数据库过滤后，我们发现了杂合的错义PDE3A变体（c.1346G> A，p.Gly449Asp）。该变体在ExAC数据库中不存在，并且位于报告的PDE3A致病变体的高度进化保守的簇中。重要的，通过SIFT（得分= 0）和PolyPhen-2（得分= 1）预测该变体会影响蛋白质功能。经过Sanger测序后，确定该先证者的健康父母以及800个种族和地理位置相匹配的健康对照都没有该变异。我们提出了一项报告，将从头开始的PDE3A变异体与常动型E型综合征的常染色体显性高血压联系起来。