Identification and characterization of genetic factors contributing to inherited tubulointerstitial kidney disease
Project goals
Autosomal dominant tubuloinsterstitial kidney diseases (ADTKD) are characterized by autosomal dominant inheritance, pathologic tubular changes and interstitial fibrosis resulting in slowly progressive chronic kidney disease. There are four major conditions as cause of ADTKD: mutation in UMOD, REN, MUC1 or SEC61A1 gene. There are still 35% of ADTKD cases with unknown ethiology. The rate of progression is very variable in individual patients between as well as within families – something that is not yet understood – with individuals requiring renal replacement therapy between the 3rd and 5th decades of life. The aim of the project is to screen families for established genetic causes, to identify genetic and molecular origin of the disease in ADTKD families, to identify genetic factors affecting progression of the disease in individual patients and to develop methods for noninvasive diagnosis and treatment follow up of these conditions. The project should enhance knowledge on ADTKD, determine the pathophysiology, and most importantly, find cures for these conditions.
Keywords
sekvenování nové generaceNext generation sequencingchronické onemocnění ledvinchronic kidney diseaseLedvinynefropatiedědičné tubulointersticiální nefropatievazebná analýzaanalýza DNAKidneynephropathyinherited tubulointerstitial nephropathylinkage analysisDNA analysis
Public support
Provider
Ministry of Health
Programme
Programme to support medical applied research in 2015 to 2022
Call for proposals
Zdravotnický AV 3 (SMZ0201701)
Main participants
Univerzita Karlova / 1. lékařská fakulta
Contest type
VS - Public tender
Contract ID
17-29786A
Alternative language
Project name in Czech
Identifikace a charakterizace genetických faktorů dědičného tubulointersticiálního onemocnění ledvin
Annotation in Czech
Autosomálně dominantní tubulointersticiální onemocnění ledvin (ADTKD) zahrnují vzácná pomalu progredující onemocnění ledvin, jež vedou ve 3.–5. dekádě života k renální insuficienci vyžadující transplantaci ledvin. Dosud známé kauzální geny UMOD, MUC1, REN a SEC61A1 objasňují genetickou příčinu u 65% případů s ADTKD. Projekt je založen na systematickém vyhledávání vzácných genetických variant v rodinách a sporadických případech s evidentně geneticky podmíněnou ADTKD, následné molekulárně biologické charakterizaci nalezených genetických variant a definici základních biologicko-patologických procesů spojených se studovanými fenotypy. Dosažených výsledků bude využito k charakterizaci genetických faktorů ovlivňujících věk nástupu a progresi postižení ledvin v jednotlivých rodinách a u jednotlivých pacientů. Zároveň budou výsledky sloužit ke správné a včasné diagnose, prevenci, cílené terapii a snížení morbidity a mortality spojené s tímto typem onemocnění.
Scientific branches
R&D category
AP - Applied research
CEP classification - main branch
EB - Genetics and molecular biology
CEP - secondary branch
—
CEP - another secondary branch
—
10603 - Genetics and heredity (medical genetics to be 3)
10604 - Reproductive biology (medical aspects to be 3)
10605 - Developmental biology
10608 - Biochemistry and molecular biology
10609 - Biochemical research methods
30101 - Human genetics
Completed project evaluation
Provider evaluation
V - Vynikající výsledky projektu (s mezinárodním významem atd.)
Project results evaluation
Aims of the project were indentification and characterization of genetic factors in Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) and to investigate the basic biological principles associated with genetic variants and their role to renal function. Rare genetic variants were systematicaly detected in families and among sporadic cases with known ADTKD during study period. Accurate molecular-biological assessments and basic pathological characteristics were analyzed in different fenotypes. Targeted genom sequencing of known genes associated with ADTKD was used. The study cohort with a highest number of patients and their families was created during study. Genetic cause of ADTKD was confirmed in 219 cases from 73 families (22%). Main benefit of the project is better knowledge of ADTKD genetic background leading to more accurate diagnostic and clinical characterization, improved genetic counselling and selection of donors for transplantation in affected families. Targeted stu
Solution timeline
Realization period - beginning
Apr 1, 2017
Realization period - end
Dec 31, 2020
Project status
U - Finished project
Latest support payment
Jun 28, 2018
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP21-MZ0-NV-U/03:1
Data delivery date
Jun 25, 2021
Finance
Total approved costs
11,703 thou. CZK
Public financial support
11,703 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
0 thou. CZK
Recognised costs
11 703 CZK thou.
Public support
11 703 CZK thou.
0%
Provider
Ministry of Health
CEP
EB - Genetics and molecular biology
Solution period
01. 04. 2017 - 31. 12. 2020