6533b862fe1ef96bd12c6ef9
RESEARCH PRODUCT
Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis
Maria Belar OrtegaLaurent DanielRosário StoneNicole LaurentJonathan A. BernsteinNicolas ChassaingDamien BrackmanRalph J. DeberardinisAudrey PawtowskiChristelle ThauvinMarie Christine MachetDeborah BartholdiJohn TolmieFabienne PrieurAnnie MichaudKatherine LachlanPhilippe LabruneDominique BonneauCarola SalorantaClarisse BaumannMarie Claire GublerSui YuJean Pierre RivièreAmir PelegJean Luc AlessandriAlix ClemensonGéraldine ViotCarol L. ClericuzioNicole PicardSatu-leena SallinenAnne Lise DelezoideMartin BitzanNancy BravermanSophie BlessonChantal LoiratChristelle ArrondelHelen V. FirthHarald GasparJulia TantauAlbert DavidSilvia MajoreAnnie Levy-mozziconacciStéphane TriauFrançois CartaultCorinne AntignacOlivier GribouvalVincent MorinièreDiana WellesleyBérénice DorayPierre CorvolSylvie CloarecJulian R. SampsonDavid ChitayatLotte Nylandsted KroghAhmed Alfaressubject
medicine.medical_specialty2716 Genetics (clinical)10039 Institute of Medical GeneticsAngiotensinogen030232 urology & nephrologyGenes RecessivePrenatal diagnosis610 Medicine & healthPeptidyl-Dipeptidase ABiologymedicine.disease_causeReceptor Angiotensin Type 1Kidney Tubules ProximalRenin-Angiotensin System03 medical and health sciences0302 clinical medicine1311 GeneticsInternal medicineReninRenin–angiotensin systemGeneticsmedicineAnimalsHumansGenetic Association StudiesGenetics (clinical)030304 developmental biology0303 health sciencesKidneyMutationAngiotensin II receptor type 1medicine.disease3. Good healthDisease Models Animalmedicine.anatomical_structureEndocrinologyUrogenital AbnormalitiesRenal blood flowMutation570 Life sciences; biologyAnuriamedicine.symptomPotter sequencedescription
Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuria, pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two-thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS in the maintenance of blood pressure and renal blood flow during the life of a human fetus. Renal hypoperfusion, whether genetic or secondary to a variety of diseases, precludes the normal development/ differentiation of proximal tubules. The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allow genetic counseling and early prenatal diagnosis.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-01-01 |