Kidney Week

Abstract: SA-PO796

Rapid Nephrogenomics in Intensive Care for Early Intervention in Adult Thrombotic Microangiopathies

Session Information

• Genetic Diseases: Glomerulopathies - II
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Yousfi, Nadhir, INSERM-Sorbonne Université UMRS 1155, Paris, France

Nadhir Yousfi,

• Mille, Marie, SeqOne Genomics, Montpellier, France

Marie Mille,

• Hamza, Abderaouf, Institut Curie, Paris, Île-de-France, France

Abderaouf Hamza,

• Vandermeersch, Sophie, INSERM-Sorbonne Université UMRS 1155, Paris, France

Sophie Vandermeersch,

• Beaumeunier, Sacha, SeqOne Genomics, Montpellier, France

Sacha Beaumeunier,

• Bertrand, Denis, SeqOne Genomics, Montpellier, France

Denis Bertrand,

• Blum, Michael, SeqOne Genomics, Montpellier, France

Michael Blum,

• Doudement, Julien, SeqOne Genomics, Montpellier, France

Julien Doudement,

• El Sissy, Carine, Hopital Europeen Georges Pompidou, Paris, Île-de-France, France

Carine El Sissy,

• Vieira-Martins, Paula, Hopital Europeen Georges Pompidou, Paris, Île-de-France, France

Paula Vieira-Martins,

• Philippe, Nicolas, SeqOne Genomics, Montpellier, France

Nicolas Philippe,

• Fremeaux Bacchi, Veronique, Hopital Europeen Georges Pompidou, Paris, Île-de-France, France

Veronique Fremeaux Bacchi,

• Mesnard, Laurent, INSERM-Sorbonne Université UMRS 1155, Paris, France

Laurent Mesnard,

Background

Nephrogenomics, represents the study of genetic factors influencing kidney function and diseases. The field has rapidly advanced in recent years due to the development of high-throughput sequencing technologies such as next-generation sequencing (NGS). Thrombotic microangiopathy (TMA) encompasses various genetically driven diseases with some of them could benefit from early intervention (C5 blocking, VitB12 therapy). Structural variants (SV) in the CFH/CFHR gene region leading to the formation of gene fusions constitute a specific molecular diagnostic bottleneck associated with 5% of complement dependent TMA (c-TMA) cases. However, the highly repetitive character of sequences in this region, makes it difficult to detect these SVs when using standard short-read sequencing. Our current turn-around time for the diagnosis of TMA (3 weeks) is too long in some clinical context. Ultra-fast sequencing techniques using long reads Nanopores technologies can provide efficient and versatile cost-effective analysis in a matter of hours.

Methods

Here we report diagnostic results of Nanopore sequencing with adaptive sampling in TMA, which is a method to enrich sequences or genes of interest. We lower our TAT to 5 days with long reads sequencing and adaptive sampling. We established a rapid molecular diagnosis that allows time-decision making on the use of anti-C5 treatment for complement-mediated TMA (c-TMA), as averting unnecessary costly and potentially harmful therapy in patients who will in any case not respond to the anti-C5 treatment.

Results

With rapid and long reads sequencing, we were able to diagnosis a case of independent complement-TMA with a variant in MMACHC. We also retrospectively validated the detection of known SVs in four samples on which MLPA (Gold standard method to identify SV) analysis was performed. We were able to detect all the SVs in these samples such as CFH-CFHR1 hybrid, CFHR1-CFH hybrids of different sizes and a deletion of CFHR1-CFHR3.

Conclusion

Thus, rapid genomics using nanopore technologies can provide valuable insights into disease detection and treatment efficacy improving patient diagnosis and prognostic, enabling optimal and early therapeutic intervention.

Funding

• Government Support – Non-U.S.