Exome sequencing reveals a de novo PRKG1 mutation in a sporadic patient with aortic dissection

BMC Medical Genetics

Zhao Liu¹  Qian Han¹  Wenwen Zhang²  Weimin Zhou²  Wei Zhou²  Qing Cao³ 

[1] Department of Vascular Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School;Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University;Key Laboratory of Molecular Medicine of Jiangxi Province;

关键词: Aortic dissection;    PRKG1 gene;    Whole-exome sequencing;    Binding motif;   

DOI  :  10.1186/s12881-018-0735-1

来源: DOAJ

【 摘 要 】

Abstract Background Thoracic 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 presentation We described a 53 years 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.1108 G > 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. Conclusions Our 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.

【 授权许可】

Unknown