Non-collagen genes role in digenic Alport syndrome

BMC Nephrology
S DagaA M Pinto

Abstract

Alport syndrome is a clinically heterogeneous nephropathy characterized by severe symptomatology at kidney level due to ultrastructural lesions of the glomerular basement membrane (GBM) as consequence of mutations in COL4 genes. The disease has been linked to COL4A3/COL4A4/COL4A5 mutations, which impair GBM functionality and can be inherited in a dominant, recessive or X-linked transmission. Although a targeted Next Generation Sequencing approach has allowed identifying families with pathogenic mutations in more than one COL4 α3-α4-α5 heterotrimer encoding genes, leading to conclude for a digenic pattern of inheritance, the role of non-collagen genes in digenic Alport syndrome has not yet been established. We employed a whole-exome sequencing approach on three families in whom a digenic pattern of transmission could be suspected because of a likely biparental contribution or an unexplained phenotype in the proband. We identified in the three probands hypomorphic LAMA5 mutations co-inherited with pathogenic COL4 α4-α5 chains mutations. Segregation analysis revealed that the combination of LAMA5/COL4 variants co-segregate with a fully penetrant phenotype in line with a digenic inheritance. In one of the three probands an hypomorp...Continue Reading

References

Oct 29, 1988·Lancet·F A FlinterM Bobrow
Apr 1, 1985·Kidney International·J FeingoldJ P Grünfeld
Oct 24, 2000·Kidney International·F T van der LoopH J Smeets
Nov 1, 1958·A.M.A. Archives of Internal Medicine·G T PERKOFFF H TYLER
Feb 13, 2010·Journal of the American Society of Nephrology : JASN·Seth GoldbergJeffrey H Miner
Mar 19, 1927·British Medical Journal·A C Alport
Jan 13, 2015·Journal of Medical Genetics·Maria Antonietta MencarelliAlessandra Renieri
Mar 6, 2015·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Rachel LennonAdrian S Woolf
Nov 20, 2016·Clinical Genetics·C FalleriniF Ariani

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Citations

Aug 11, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Susan L MurrayPeter J Conlon
Jul 28, 2020·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Clifford E Kashtan
May 25, 2021·American Journal of Physiology. Renal Physiology·Liang NingJeffrey H Miner
Jan 29, 2022·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Yasar Caliskan, Krista L Lentine

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Methods Mentioned

BETA
exome sequencing
biopsy
biopsies

Software Mentioned

Mutation Assessor
Mutation Taster
SpliceSiteFinder - like
FATHMM
SIFT
IonTorrent Suite
Human Splicing Finder
Torrent Variant Caller
Polyphen
Alamut

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