Human and mouse studies establish TBX6 in Mendelian CAKUT and as a potential driver of kidney defects associated with the 16p11.2 microdeletion syndrome.
16p11.2 deletion
CNV
allelic series
compound inheritance
gene dosage
gene expression
kidney development
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
22
08
2019
revised:
03
03
2020
accepted:
09
04
2020
pubmed:
26
5
2020
medline:
22
6
2021
entrez:
26
5
2020
Statut:
ppublish
Résumé
Congenital anomalies of the kidney and urinary tract (CAKUTs) are the most common cause of chronic kidney disease in children. Human 16p11.2 deletions have been associated with CAKUT, but the responsible molecular mechanism remains to be illuminated. To explore this, we investigated 102 carriers of 16p11.2 deletion from multi-center cohorts, among which we retrospectively ascertained kidney morphologic and functional data from 37 individuals (12 Chinese and 25 Caucasian/Hispanic). Significantly higher CAKUT rates were observed in 16p11.2 deletion carriers (about 25% in Chinese and 16% in Caucasian/Hispanic) than those found in the non-clinically ascertained general populations (about 1/1000 found at autopsy). Furthermore, we identified seven additional individuals with heterozygous loss-of-function variants in TBX6, a gene that maps to the 16p11.2 region. Four of these seven cases showed obvious CAKUT. To further investigate the role of TBX6 in kidney development, we engineered mice with mutated Tbx6 alleles. The Tbx6 heterozygous null (i.e., loss-of-function) mutant (Tbx6
Identifiants
pubmed: 32450157
pii: S0085-2538(20)30547-0
doi: 10.1016/j.kint.2020.04.045
pmc: PMC7673260
mid: NIHMS1597079
pii:
doi:
Substances chimiques
T-Box Domain Proteins
0
TBX6 protein, human
0
Tbx6 protein, mouse
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
1020-1030Subventions
Organisme : NIDDK NIH HHS
ID : P20 DK116191
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006542
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS105078
Pays : United States
Organisme : NHGRI NIH HHS
ID : K08 HG008986
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK103184
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115574
Pays : United States
Informations de copyright
Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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