Kidney international reports · 2026
Exome Sequencing in Patients with Loin Pain Hematuria Syndrome and Persistent Isolated Hematuria.
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Prasad Bhanu, Soliman Ahmed M, Garg Aarti, Sharma Aditi, Schott Clara, Connaughton Dervla, Lanktree Matthew B
Аннотация
INTRODUCTION: Loin pain hematuria syndrome (LPHS) is characterized by chronic loin pain and hematuria without a urological cause. We hypothesized that rare genetic variants in genes impacting the glomerular filtration barrier (endothelial cells, glomerular basement membrane, or podocytes) may contribute to LPHS.
METHODS: Exome sequencing was performed in 29 consecutive patients; 17 with LPHS, and 12 with persistent painless isolated hematuria (IH). We first evaluated a virtual gene panel of 130 hematuria-linked genes curated from the literature followed by an exome-wide analysis. Variant interpretation was performed using clinical criteria.
RESULTS: Of 17 patients with LPHS, 13 had gross hematuria, 4 had microscopic hematuria, all with chronic pain. Of these, 9 had a history of kidney stones, but none had obstruction on current imaging; 8 had a family history of kidney stones, 3 of hematuria, and 2 of LPHS. Of 17 patients with LPHS, 4 (23%) had a heterozygous pathogenic or likely pathogenic (P/LP) variant-1 in each of COL4A4, MSTO1, FLNA, and APPL1. Of 12 patients with IH, 4 (33%) with painless hematuria had a P/LP variant-1 in each of COL4A3, COL4A5, FLNA, and UQCRC1. Broadening to include the whole exome, no additional P/LP variants believed to be involved in LPHS were identified.
CONCLUSIONS: LPHS appears to be the result of multiple heterogeneous mechanisms. Our analysis did not identify a common monogenic cause, but rare variants were observed in multiple genes among affected individuals. Pathogenic variants in type IV collagen genes (COL4A3-5) were identified in 1 of 17 patients with LPHS and 2 of 12 patients with IH.
METHODS: Exome sequencing was performed in 29 consecutive patients; 17 with LPHS, and 12 with persistent painless isolated hematuria (IH). We first evaluated a virtual gene panel of 130 hematuria-linked genes curated from the literature followed by an exome-wide analysis. Variant interpretation was performed using clinical criteria.
RESULTS: Of 17 patients with LPHS, 13 had gross hematuria, 4 had microscopic hematuria, all with chronic pain. Of these, 9 had a history of kidney stones, but none had obstruction on current imaging; 8 had a family history of kidney stones, 3 of hematuria, and 2 of LPHS. Of 17 patients with LPHS, 4 (23%) had a heterozygous pathogenic or likely pathogenic (P/LP) variant-1 in each of COL4A4, MSTO1, FLNA, and APPL1. Of 12 patients with IH, 4 (33%) with painless hematuria had a P/LP variant-1 in each of COL4A3, COL4A5, FLNA, and UQCRC1. Broadening to include the whole exome, no additional P/LP variants believed to be involved in LPHS were identified.
CONCLUSIONS: LPHS appears to be the result of multiple heterogeneous mechanisms. Our analysis did not identify a common monogenic cause, but rare variants were observed in multiple genes among affected individuals. Pathogenic variants in type IV collagen genes (COL4A3-5) were identified in 1 of 17 patients with LPHS and 2 of 12 patients with IH.