A Founder Mutation in
Adolescent
Adult
Animals
Child
Child, Preschool
Deafness
/ genetics
Endocytosis
Humans
Kidney Tubules, Proximal
/ metabolism
Low Density Lipoprotein Receptor-Related Protein-2
/ genetics
Mice
Mutation
Proteinuria
/ metabolism
Vesicular Transport Proteins
/ genetics
Young Adult
Zebrafish
/ metabolism
Eps15 homology domain
epithelial transport physiology
genetic renal disease
infertility
megalin
mutation
proximal tubule
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
06
10
2021
accepted:
17
12
2021
pubmed:
13
2
2022
medline:
5
4
2022
entrez:
12
2
2022
Statut:
ppublish
Résumé
The endocytic reabsorption of proteins in the proximal tubule requires a complex machinery and defects can lead to tubular proteinuria. The precise mechanisms of endocytosis and processing of receptors and cargo are incompletely understood. EHD1 belongs to a family of proteins presumably involved in the scission of intracellular vesicles and in ciliogenesis. However, the relevance of EHD1 in human tissues, in particular in the kidney, was unknown. Genetic techniques were used in patients with tubular proteinuria and deafness to identify the disease-causing gene. Diagnostic and functional studies were performed in patients and disease models to investigate the pathophysiology. We identified six individuals (5-33 years) with proteinuria and a high-frequency hearing deficit associated with the homozygous missense variant c.1192C>T (p.R398W) in A homozygous missense variant of
Sections du résumé
BACKGROUND
The endocytic reabsorption of proteins in the proximal tubule requires a complex machinery and defects can lead to tubular proteinuria. The precise mechanisms of endocytosis and processing of receptors and cargo are incompletely understood. EHD1 belongs to a family of proteins presumably involved in the scission of intracellular vesicles and in ciliogenesis. However, the relevance of EHD1 in human tissues, in particular in the kidney, was unknown.
METHODS
Genetic techniques were used in patients with tubular proteinuria and deafness to identify the disease-causing gene. Diagnostic and functional studies were performed in patients and disease models to investigate the pathophysiology.
RESULTS
We identified six individuals (5-33 years) with proteinuria and a high-frequency hearing deficit associated with the homozygous missense variant c.1192C>T (p.R398W) in
CONCLUSIONS
A homozygous missense variant of
Identifiants
pubmed: 35149593
pii: 00001751-202204000-00011
doi: 10.1681/ASN.2021101312
pmc: PMC8970462
doi:
Substances chimiques
EHD1 protein, human
0
Low Density Lipoprotein Receptor-Related Protein-2
0
Vesicular Transport Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
732-745Subventions
Organisme : Wellcome Trust
ID : 203141/Z/16/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 by the American Society of Nephrology.
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