Rapid nephrogenomics for thrombotic microangiopathies

Abstract

Our work underscores the feasibility and impact of swift genomic analysis via nanopore sequencing with adaptive sampling for the management of thrombotic microangiopathies (TMAs), a rare genetic condition in which molecular diagnosis can guide therapeutics. We demonstrate that diagnoses can be achieved in less than three days with hybrid complement factor H/complement factor H receptor gene detection within the same assay. Hybrid genes cannot be detected by short-read sequencing. This is in line with our previous study, in which we exemplified the utility of short-read exome sequencing for TMA and large-scale screening, with a turnaround time of weeks. Our current work represents a significant advancement beyond this, describing 18 prospective TMA cases with a molecular diagnosis made in the short timeframe of three days.

Biography

Professor Laurent Mesnard is Head of the Intensive Care Nephrology Unit at Assistance Publique Hopitaux de Paris Tenon Hospital, Sorbonne University, Paris, and a national coordinator for the French National plan of sequencing (PFMG2025) for rare adult kidney diseases. He co-coordinates the National Thrombotic Microangiopathies network (CNR-MAT). Prof. Mesnard’s team, located in Paris, use short-read whole-exome/genome sequencing for the clinical diagnosis of adult chronic kidney disease. They also develop applications for long-read sequencing technologies to accelerate clinical diagnosis for rare kidney diseases at their ICU admission. Another project (Allogenomics) aims to develop new metrics to evaluate the risk of chronic kidney graft failure and better allocation strategies for kidney transplantation.