Coinheritance of COL4A5 and MYO1E mutations accentuate the severity of kidney disease.

Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
Rachel LennonAdrian S Woolf

Abstract

Mutations in podocyte and basement membrane genes are associated with a growing spectrum of glomerular disease affecting adults and children. Investigation of familial cases has helped to build understanding of both normal physiology and disease. We investigated a consanguineous family with a wide clinical phenotype of glomerular disease using clinical, histological, and new genetic studies. We report striking variability in severity of nephropathy within an X-linked Alport syndrome (XLAS) family. Four siblings each carried a mutant COL4A5 allele, p.(Gly953Val) and p.(Gly1033Arg). Two boys had signs limited to hematuria and mild/moderate proteinuria. In striking contrast, a sister presented with end-stage renal disease (ESRD) at 8 years of age and an infant brother presented with nephrotic syndrome, progressing to ESRD by 3 years of age. Both were subsequently found to have homozygous variants in MYO1E, p.(Lys118Glu) and p.(Thr876Arg). MYO1E is a gene implicated in focal segmental glomerulosclerosis and it encodes a podocyte-expressed non-muscle myosin. Bioinformatic modeling demonstrated that the collagen IV-alpha3,4,5 extracellular network connected via known protein-protein interactions to intracellular myosin 1E. COL4A5 and...Continue Reading

References

Nov 17, 2007·Bioinformatics·Yassen AssenovMario Albrecht
Dec 17, 2008·Nature Methods·Jianmin WuSampsa Hautaniemi
May 28, 2009·Journal of the American Society of Nephrology : JASN·Laurence Heidet, Marie-Claire Gubler
Dec 8, 2009·Clinical Journal of the American Society of Nephrology : CJASN·Rachel TanJudy Savige
Apr 23, 2010·Journal of Cell Science·Ronen Zaidel-Bar, Benjamin Geiger
Mar 19, 1927·British Medical Journal·A C Alport
Oct 5, 2010·Clinical Journal of the American Society of Nephrology : CJASN·Helen HansonFrances Flinter
Feb 3, 2011·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Nicholas J A WebbCéline Le Bailly De Tilleghem
Jul 16, 2011·The New England Journal of Medicine·Caterina MeleUNKNOWN PodoNet Consortium
Sep 13, 2011·American Journal of Medical Genetics. Part a·Joanna McCauleySimon T Holden
Jan 10, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Konstantinos VoskaridesConstantinos Deltas
Jul 20, 2012·American Journal of Physiology. Renal Physiology·Sharon E ChaseMira Krendel
Jan 26, 2013·Journal of the American Society of Nephrology : JASN·Judy SavigeFrances Flinter
Jan 26, 2013·Clinical Journal of the American Society of Nephrology : CJASN·Hugh J McCarthyUNKNOWN RADAR the UK SRNS Study Group
Apr 19, 2013·Journal of Human Genetics·Mohamed H Al-HamedBrian F Meyer
Sep 21, 2013·Journal of the American Society of Nephrology : JASN·Helen StoreyFrances A Flinter
Dec 18, 2013·Journal of Cellular Biochemistry·Xia JinLizhong Du
Jan 18, 2014·Journal of the American Society of Nephrology : JASN·Rachel LennonMartin J Humphries
Jan 28, 2014·Experimental Cell Research·Jessica L Ouderkirk, Mira Krendel

❮ Previous
Next ❯

Citations

Sep 29, 2015·Clinical Kidney Journal·Hans-Joachim AndersBrad Rovin
Nov 18, 2015·Seminars in Nephrology·Georg Lorenz, Hans-Joachim Anders
Nov 4, 2016·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Judy Savige
Oct 12, 2016·Scientific Reports·Michael J RandlesRachel Lennon
Nov 1, 2016·Clinical and Experimental Nephrology·Kana YokotaKazumoto Iijima
Aug 1, 2019·Molecular Genetics & Genomic Medicine·Tomohiko YamamuraKazumoto Iijima
Sep 15, 2019·Molecular Genetics and Genomics : MGG·Mara Sanches GuaragnaMaricilda Palandi de Mello
Oct 5, 2017·Clinical Genetics·C Deltas
Feb 28, 2019·BMC Nephrology·S DagaA M Pinto
May 31, 2019·Molecular Genetics & Genomic Medicine·Shunlai ShangXiang M Chen
May 3, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Michelle N RheaultRachel Lennon
Jun 30, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Erol Demir, Yasar Caliskan
Jul 11, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Judy SavigeHelen Storey
Oct 4, 2020·The Journal of Pathology·Jin-Ju Kim, Alessia Fornoni
Jul 28, 2020·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Clifford E Kashtan

❮ Previous
Next ❯

Methods Mentioned

BETA
XLAS
exome sequencing
PCR
biopsy
biopsies
light microscopy

Software Mentioned

NetworkAnalyzer
Cytoscape
Alamut
SAMtools
MatrixDB
Annovar
Novoalign

Related Concepts

Related Feeds

Basement Membranes

Basement membranes are thin, specialized extracellular matrices surrounding most tissues in all metazoans. Here is the latest research on basement membranes.

Related Papers

Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
Julia HoefeleLutz T Weber
The New England Journal of Medicine
Caterina MelePodoNet Consortium
Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
Hyun Kyung LeeHae Il Cheong
BMC Nephrology
Genevieve Pont-KingdonElaine Lyon
© 2022 Meta ULC. All rights reserved