Exome sequencing reveals a de novo PRKG1 mutation in a sporadic patient with aortic dissection
Exome sequencing reveals a de novo PRKG1 mutation in a sporadic patient with aortic dissection
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DOI：
10.1186/s12881-018-0735-1
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发表时间：
2018-12-22
影响因子：
--
通讯作者：
Zhou, Weimin
中科院分区：
文献类型：
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作者：
Zhang, Wenwen;Han, Qian;Zhou, Weimin
胸主动脉瘤和夹层（TAAD）是一种常见病，死亡率高。它主要以常染色体显性方式遗传，具有降低的遗传率和可变的表达。大多数TAAD病例的遗传基础仍然未知。病例介绍我们描述了一位53岁男性，患有腹主动脉夹层和主动脉迂曲。为了研究临床表现的遗传基础，进行了全外显子组测序。外显子组测序鉴定了PRKG1基因中的未描述的从头杂合突变（NM_001098512.2：c.1108G>A），预测其导致蛋白质的ATP结合基序中的错义改变p.Gly370Ser。该突变在dbSNP、1000 Genome Project和Exome测序数据库中未报道。此外，PRKG1的甘氨酸370残基在各种物种中高度保守，并且预测它会被多个计算机程序破坏，这表明这种取代可能导致蛋白质功能的重大破坏。据我们所知，这是第二个报告的突变位点的PRKG1占disease.ConclusionsOur研究扩大了突变谱的PRKG1和突变携带者的临床表型。在患有不明原因的主动脉疾病的患者中应考虑筛查PRKG1突变，并且鉴定致病基因将有助于个体化，基因定制管理。
BackgroundThoracic aortic aneurysm and dissection (TAAD) is a common condition associated with high mortality. It is predominantly inherited in an autosomal dominant manner with reduced penetrance and variable expression. The genetic basis of the majority of TAAD cases remains unknown.Case presentationWe described a 53years old male presented with abdominal aortic dissection as well as aortic tortuosity. To investigate the genetic basis of the clinical presentation, whole-exome sequencing was performed. Exome sequencing identified a de novo heterozygous undescribed mutation in the PRKG1 gene (NM_001098512.2: c.1108G>A), predicted to cause the missense change p.Gly370Ser in the ATP binding motif of the protein. This mutation was not reported in the dbSNP, 1000 Genome Project, and Exome sequencing databases. Furthermore, the Glycine370 residue of PRKG1 is highly conserved among various species and it is predicted to be damaging by multiple in silico programs, suggesting that this substitution may cause a major disruption of protein function. To our knowledge, this is the second reported mutation locus of PRKG1 accounting for the disease.ConclusionsOur study expands the mutation spectrum of PRKG1 and clinical phenotype of mutation-carriers. Screening for PRKG1 mutations should be considered in patients with unexplained aortic disease, and identification of the causative gene will aid in individualized, gene-tailored management.