A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G > A (IVS25+1G > A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

A Persu, M Lambert, J (Jacob) Deinum, M Cossu, L Irenge, J Ambroise, JM Minon, AB Nesterovitch, A Churbanov, IA Popova, SM Danilov, Jan Danser, JL Gala, N Visscher

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)
8 Downloads (Pure)

Abstract

Background: Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results: Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or c Conclusions: We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences.
Original languageUndefined/Unknown
JournalPLoS One (print)
Volume8
Issue number4
DOIs
Publication statusPublished - 2013

Research programs

  • EMC COEUR-09

Cite this