Copy number variation analysis in 138 families with steroid-resistant nephrotic syndrome identifies causal homozygous deletions in PLCE1 and NPHS2 in two families.

Autor: Pantel D; Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA.; Institute of Human Genetics, Heidelberg University, Heidelberg, Germany., Mertens ND; Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA., Schneider R; Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA., Hölzel S; Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA., Kari JA; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Pediatric Nephrology Center of Excellence, King Abdulaziz University Hospital, Jeddah, Saudi Arabia., Desoky SE; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Pediatric Nephrology Center of Excellence, King Abdulaziz University Hospital, Jeddah, Saudi Arabia., Shalaby MA; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Pediatric Nephrology Center of Excellence, King Abdulaziz University Hospital, Jeddah, Saudi Arabia., Lim TY; Division of Nephrology, Department of Medicine, Columbia University, New York, NY, USA., Sanna-Cherchi S; Division of Nephrology, Department of Medicine, Columbia University, New York, NY, USA., Shril S; Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA., Hildebrandt F; Division of Nephrology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA. friedhelm.hildebrandt@childrens.harvard.edu.
Jazyk: angličtina
Zdroj: Pediatric nephrology (Berlin, Germany) [Pediatr Nephrol] 2024 Feb; Vol. 39 (2), pp. 455-461. Date of Electronic Publication: 2023 Sep 05.
DOI: 10.1007/s00467-023-06134-2
Abstrakt: Background: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of kidney failure in children and adults under the age of 20 years. Previously, we were able to detect by exome sequencing (ES) a known monogenic cause of SRNS in 25-30% of affected families. However, ES falls short of detecting copy number variants (CNV). Therefore, we hypothesized that causal CNVs could be detected in a large SRNS cohort.
Methods: We performed genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on a cohort of 138 SRNS families, in whom we previously did not identify a genetic cause through ES. We evaluated ES and CNV data for variants in 60 known SRNS genes and in 13 genes in which variants are known to cause a phenocopy of SRNS. We applied previously published, predefined criteria for CNV evaluation.
Results: We detected a novel CNV in two genes in 2 out of 138 families (1.5%). The 9,673 bp homozygous deletion in PLCE1 and the 6,790 bp homozygous deletion in NPHS2 were confirmed across the breakpoints by PCR and Sanger sequencing.
Conclusions: We confirmed that CNV analysis can identify the genetic cause in SRNS families that remained unsolved after ES. Though the rate of detected CNVs is minor, CNV analysis can be used when there are no other genetic causes identified. Causative CNVs are less common in SRNS than in other monogenic kidney diseases, such as congenital anomalies of the kidneys and urinary tract, where the detection rate was 5.3%. A higher resolution version of the Graphical abstract is available as Supplementary information.
(© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)
Databáze: MEDLINE
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