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. 2023 Jul 3:10:20543581231183856.
doi: 10.1177/20543581231183856. eCollection 2023.

Basic Research Protocol: Exome Sequencing in Adults With Loin Pain Hematuria Syndrome: A Pilot Study

Aditi Sharma  1 , Matthew B Lanktree  2   3 , Sarah Liskowich  4 , Pouneh Dokouhaki  5 , Bhanu Prasad  6   7
Affiliations

Basic Research Protocol: Exome Sequencing in Adults With Loin Pain Hematuria Syndrome: A Pilot Study

Aditi Sharma et al. Can J Kidney Health Dis. .

Abstract
in English, French

Background: Loin pain hematuria syndrome (LPHS) is a poorly understood clinical syndrome characterized by hematuria and either unilateral or bilateral severe kidney pain in the absence of identifiable urological disease. Loin pain hematuria syndrome imposes a significant health and economic impact with a loss of productivity and quality of life in a young population. Owing to an incomplete understanding of its pathophysiology, treatment has been limited to nonspecific pain management. Nearly 60 years after its initial description, we are no further ahead in understanding the molecular pathways involved in LPHS.

Objective: To outline the study design for exome sequencing in adults with LPHS and their families.

Methods: In this single-center case series, 24 patients with LPHS and 2 additional first-degree family members per participant will be recruited. DNA extracted from venous blood samples will undergo exome sequencing on the Illumina NovaSeq 6000 System at 100× depth and will be assessed for pathogenic variants in genes associated with hematuria (number of genes in: glomerular endothelium [n = 10] and basement membrane [n = 8]), and pain pathways (number of genes in: pain transduction [n = 17], conduction [n = 8], synaptic transmission [n = 37], and modulation [n = 27]). We will further examine identified potentially pathogenic variants that co-segregate with LPHS features among affected families.

Conclusions: This pilot study may identify new directions for an investigation into the molecular mechanisms underlying LPHS.

Contexte: Le syndrome de lombalgie-hématurie est un syndrome clinique encore mal compris qui se caractérise par une hématurie et une forte douleur rénale unilatérale ou bilatérale en l’absence d’une maladie urologique identifiable. Le syndrome de lombalgie-hématurie a une incidence importante sur la santé et l’économie en entraînant une perte de productivité et de qualité de vie dans une population jeune. La compréhension de la physiopathologie de ce syndrome étant incomplète, le traitement a été limité à la gestion non spécifique de la douleur. Près de soixante ans après sa description initiale, nous en sommes au même point dans la compréhension des voies moléculaires impliquées dans le syndrome de lombalgie-hématurie.

Objectif: Décrire le plan de l’étude pour le séquençage de l’exome chez les adultes atteints du syndrome de lombalgie-hématurie et des membres de leur famille.

Méthodologie: Pour cette série de cas menée dans un seul center, nous recruterons 24 patients atteints du syndrome de lombalgie-hématurie et deux membres au premier degré de leur famille. L’ADN extrait d’échantillons de sang veineux sera soumis à un séquençage de l’exome sur le système Ilumina NovaSeq 6000 réglé à 100X de profondeur. Il sera également analysé pour la présence de variants pathogènes dans les gènes associés à l’hématurie (nombre de gènes dans l’endothélium glomérulaire [n = 10] et la membrane basale [n = 8]), et aux voies de transmission de la douleur (nombre de gènes dans la transduction [n = 17], la conduction [n = 8], la transmission synaptique [n = 37] et la modulation [n = 27] de la douleur). Nous poursuivrons l’examen des variants potentiellement pathogènes identifiés qui co-ségrègent avec les caractéristiques du syndrome de lombalgie-hématurie parmi les familles touchées.

Conclusion: Cette étude pilote pourrait révéler de nouveaux axes de recherche sur les mécanismes moléculaires qui sous-tendent le syndrome de lombalgie-hématurie.

Keywords: chronic pain; eGFR; exome sequencing; hematuria; loin pain hematuria syndrome; rare disease.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BP has received speaker and advisory fees from Bayer, Otsuka and Astra Zeneca. MBL has received speaker and advisory fees from Otsuka, Reata, Bayer, and Sanofi Genzyme.

Figures

Figure 1.
Figure 1.
Study design.
Figure 2.
Figure 2.
Pedigree of LPHS patients with a family history of LPHS or isolated hematuria (IH). Roman numbers represent the generations of the family. Note. Proband is indicated by arrow. Abbreviations: k, kidney stones; m, migraine.
Figure 3.
Figure 3.
Pipeline for exome data analysis.
See this image and copyright information in PMC

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