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Whole exome sequencing identifies KIF26B, LIFR and LAMC1 mutations in familial vesicoureteral reflux. | LitMetric

Whole exome sequencing identifies KIF26B, LIFR and LAMC1 mutations in familial vesicoureteral reflux.

PLoS One

Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Published: November 2022

AI Article Synopsis

Article Abstract

Vesicoureteral reflux (VUR) is a common urological problem in children and its hereditary nature is well recognised. However, despite decades of research, the aetiological factors are poorly understood and the genetic background has been elucidated in only a minority of cases. To explore the molecular aetiology of primary hereditary VUR, we performed whole-exome sequencing in 13 large families with at least three affected cases. A large proportion of our study cohort had congenital renal hypodysplasia in addition to VUR. This high-throughput screening revealed 23 deleterious heterozygous variants in 19 candidate genes associated with VUR or nephrogenesis. Sanger sequencing and segregation analysis in the entire families confirmed the following findings in three genes in three families: frameshift LAMC1 variant and missense variants of KIF26B and LIFR genes. Rare variants were also found in SALL1, ROBO2 and UPK3A. These gene variants were present in individual cases but did not segregate with disease in families. In all, we demonstrate a likely causal gene variant in 23% of the families. Whole-exome sequencing technology in combination with a segregation study of the whole family is a useful tool when it comes to understanding pathogenesis and improving molecular diagnostics of this highly heterogeneous malformation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683562PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0277524PLOS

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