Abstract
Beyond the major gene BMPR2, several new genes predisposing to PAH have been identified during the last decade. Recently, preliminary evidence of the involvement of the KDR gene was found in a large genetic association study.
We prospectively analysed the KDR gene by targeted panel sequencing in a series of 311 PAH patients referred to a clinical molecular laboratory for genetic diagnosis of PAH.
Two index cases with severe PAH from two different families were found to carry a loss-of-function mutation in the KDR gene. These two index cases were clinically characterised by low diffusing capacity for carbon monoxide adjusted for haemoglobin (DLCOc) and interstitial lung disease. In one family, segregation analysis revealed that variant carriers are either presenting with PAH associated with low DLCOc, or have only decreased DLCOc, whereas non-carrier relatives have normal DLCOc. In the second family, a single affected carrier was alive. His carrier mother was unaffected with normal DLCOc.
We provided genetic evidence for considering KDR as a newly identified PAH-causing gene by describing the segregation of KDR mutations with PAH in two families. In our study, KDR mutations are associated with a particular form of PAH characterised by low DLCOc and radiological evidence of parenchymal lung disease including interstitial lung disease and emphysema.
Abstract
KDR mutations were identified in two families with a particular form of PAH characterised by low DLCOc and radiological evidence of parenchymal lung disease http://bit.ly/30npPPn
Footnotes
This article has supplementary material available from erj.ersjournals.com
This article has an editorial commentary: https://doi.org/10.1183/13993003.00326-2020
Conflict of interest: M. Eyries has nothing to disclose. D. Montani reports grants and personal fees from Actelion and Bayer, personal fees from GSK, Pfizer and MSD, outside the submitted work.
Conflict of interest: B. Girerd has nothing to disclose.
Conflict of interest: N. Favrolt has nothing to disclose.
Conflict of interest: M. Riou has nothing to disclose.
Conflict of interest: L. Faivre has nothing to disclose.
Conflict of interest: G. Manaud has nothing to disclose.
Conflict of interest: F. Perros has nothing to disclose.
Conflict of interest: S. Gräf has nothing to disclose.
Conflict of interest: M.W. Morrell is an employee of Morphogen-IX.
Conflict of interest: M. Humbert reports personal fees from Acceleron, Actelion, Merck and United Therapeutics, grants and personal fees from Bayer and GSK, outside the submitted work.
Conflict of interest: F. Soubrier has nothing to disclose.
Support statement: Funding for the project was provided by the Wellcome Trust. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received November 7, 2019.
- Accepted January 2, 2020.
- Copyright ©ERS 2020