Sequence variants in the renin-angiotensin system genes are associated with isolated multicystic dysplastic kidney in children.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
07
08
2020
accepted:
22
10
2020
revised:
06
10
2020
pubmed:
12
11
2020
medline:
9
2
2022
entrez:
11
11
2020
Statut:
ppublish
Résumé
Multicystic dysplastic kidney (MCDK) is a common form of congenital cystic kidney disease in children. The etiology of MCDK remains unclear. Given an important role of the renin-angiotensin system in normal kidney development, we explored whether MCDK in children is associated with variants in the genes encoding renin-angiotensin system components by Sanger sequencing. The coding regions of renin (REN), angiotensinogen (AGT), ACE, and angiotensin 1 receptor (AGTR1) genes were amplified by PCR. The effect of DNA sequence variants on protein function was predicted with PolyPhen-2 software. 3 novel and known AGT variants were found. 1 variant was probably damaging, 1 was possibly damaging and one was benign. Out of 7 REN variants, 4 were probably damaging and 3 were benign. Of 6 ACE variants, 3 were probably damaging and 3-benign. 3 AGTR1 variants were found. 2 variants were possibly damaging, and one was benign. We report novel associations of sequence variants in REN, AGT, ACE, or AGTR1 genes in children with isolated MCDK in the United States. Our findings suggest a recessive disease model and support the hypothesis of multiple renin-angiotensin system gene involvement in MCDK. Discovery of novel gene variants in renin-angiotensin genes in children with MCDK. Novel possibly damaging gene variants discovered. Multiple renin-angiotensin system gene variants are involved in MCDK.
Sections du résumé
BACKGROUND
Multicystic dysplastic kidney (MCDK) is a common form of congenital cystic kidney disease in children. The etiology of MCDK remains unclear. Given an important role of the renin-angiotensin system in normal kidney development, we explored whether MCDK in children is associated with variants in the genes encoding renin-angiotensin system components by Sanger sequencing.
METHODS
The coding regions of renin (REN), angiotensinogen (AGT), ACE, and angiotensin 1 receptor (AGTR1) genes were amplified by PCR. The effect of DNA sequence variants on protein function was predicted with PolyPhen-2 software.
RESULTS
3 novel and known AGT variants were found. 1 variant was probably damaging, 1 was possibly damaging and one was benign. Out of 7 REN variants, 4 were probably damaging and 3 were benign. Of 6 ACE variants, 3 were probably damaging and 3-benign. 3 AGTR1 variants were found. 2 variants were possibly damaging, and one was benign.
CONCLUSION
We report novel associations of sequence variants in REN, AGT, ACE, or AGTR1 genes in children with isolated MCDK in the United States. Our findings suggest a recessive disease model and support the hypothesis of multiple renin-angiotensin system gene involvement in MCDK.
IMPACT
Discovery of novel gene variants in renin-angiotensin genes in children with MCDK. Novel possibly damaging gene variants discovered. Multiple renin-angiotensin system gene variants are involved in MCDK.
Identifiants
pubmed: 33173183
doi: 10.1038/s41390-020-01255-y
pii: 10.1038/s41390-020-01255-y
doi:
Substances chimiques
AGT protein, human
0
AGTR1 protein, human
0
Receptor, Angiotensin, Type 1
0
Angiotensinogen
11002-13-4
ACE protein, human
EC 3.4.15.1
Peptidyl-Dipeptidase A
EC 3.4.15.1
Renin
EC 3.4.23.15
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
205-211Informations de copyright
© 2020. International Pediatric Research Foundation, Inc.
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