Beyond the kidney biopsy: genomic approach to undetermined kidney diseases.

Background: According to data from large national registries, almost 20%-25% of patients with end-stage kidney disease have an undetermined kidney disease (UKD). Recent data have shown that monogenic disease-causing variants are under-diagnosed. We performed exome sequencing (ES) on UKD patients in our center to improve the diagnosis rate.

Update of the UMD-VHL database: classification of 164 challenging variants based on genotype-phenotype correlation among 605 entries.

Background: The von Hippel-Lindau (VHL) disease is a hereditary tumour syndrome caused by germline mutations in tumour suppressor gene. The identification of variants requires accurate classification which has an impact on patient management and genetic counselling.

Methods: The TENGEN (French oncogenetics network of neuroendocrine tumors) and PREDIR (French National Cancer Institute network for Inherited predispositions to kidney cancer) networks have collected genetic variants and clinical characteristics of all VHL-suspected patients analysed from 2003 to 2021 by one of the nine laboratories performing genetic testing in France.

Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis.

Introduction: Previous studies have suggested that genetic kidney diseases in adults are often overlooked, representing up to 10% of all cases of chronic kidney disease (CKD). We present data obtained from exome sequencing (ES) analysis of patients with biopsy-proven undetermined kidney disease (UKD).

Methods: ES was proposed during routine clinical care in patients with UKD from January 2020 to December 2021.

Spatial Distribution of Immune Cells in Primary and Recurrent Glioblastoma: A Small Case Study.

Only a minority of patients with glioblastoma (GBM) respond to immunotherapy, and always only partially. There is a lack of knowledge on immune distribution in GBM and in its tumor microenvironment (TME). To address the question, we used paired primary and recurrent tumors from GBM patients to study the composition and the evolution of the immune landscape upon treatment.

Protein domains provide a new layer of information for classifying human variations in rare diseases.

Using the ACMG-AMP guidelines for the interpretation of sequence variants, it remains difficult to meet the criterion associated with the protein domain, PM1, which is assigned in only about 10% of cases, whereas the criteria related to variant frequency, PM2/BA1/BS1, is reported in 50% of cases. To improve the classification of human missense variants using protein domains information, we developed the DOLPHIN system (https://dolphin.mmg-gbit.