Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome.
Adolescent
Age of Onset
Cell Line
Child
Child, Preschool
Consanguinity
DNA Mutational Analysis
Disease Progression
Drug Resistance
/ genetics
Female
Follow-Up Studies
Gene Frequency
Glomerular Basement Membrane
/ pathology
Glucocorticoids
/ pharmacology
Homozygote
Humans
Male
Membrane Proteins
/ genetics
Microscopy, Electron, Transmission
Mutation
Nephrotic Syndrome
/ drug therapy
Pedigree
Podocytes
Renal Insufficiency, Chronic
/ genetics
Exome Sequencing
KIRREL1
focal segmental glomerulosclerosis
minimal change disease
steroid-resistant nephrotic syndrome
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
31
01
2019
revised:
11
06
2019
accepted:
14
06
2019
pubmed:
2
9
2019
medline:
21
10
2020
entrez:
2
9
2019
Statut:
ppublish
Résumé
Steroid-resistant nephrotic syndrome is a frequent cause of chronic kidney disease almost inevitably progressing to end-stage renal disease. More than 58 monogenic causes of SRNS have been discovered and majority of known steroid-resistant nephrotic syndrome causing genes are predominantly expressed in glomerular podocytes, placing them at the center of disease pathogenesis. Herein, we describe two unrelated families with steroid-resistant nephrotic syndrome with homozygous mutations in the KIRREL1 gene. One mutation showed high frequency in the European population (minor allele frequency 0.0011) and this patient achieved complete remission following treatment, but later progressed to chronic kidney disease. We found that mutant KIRREL1 proteins failed to localize to the podocyte cell membrane, indicating defective trafficking and impaired podocytes function. Thus, the KIRREL1 gene product has an important role in modulating the integrity of the slit diaphragm and maintaining glomerular filtration function.
Identifiants
pubmed: 31472902
pii: S0085-2538(19)30703-3
doi: 10.1016/j.kint.2019.06.016
pmc: PMC6756928
mid: NIHMS1534144
pii:
doi:
Substances chimiques
Glucocorticoids
0
KIRREL1 protein, human
0
Kirrel1 protein, mouse
0
Membrane Proteins
0
nephrin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
883-889Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK079310
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120510
Pays : United States
Organisme : NIH HHS
ID : S10 OD018521
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK076683
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK087956
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007726
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK116887
Pays : United States
Informations de copyright
Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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