Genetics of Congenital Anomalies of the Kidney and Urinary Tract: The Current State of Play

Capone, Valentina; Morello, William; Taroni, Francesca; Montini, Giovanni

doi:10.3390/ijms18040796

Cited by 110 publications

(98 citation statements)

References 128 publications

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“…Eventually, this leads to nephron patterning and elongation. Perturbations in any part of this multistep process can lead to congenital anomalies of the urogenital tract or deficit in kidney function . Given early development of the kidneys and urinary tract, teratogens, including certain medications such as ACE inhibitors and warfarin among others (Table ), should be avoided in the first trimester.…”

Section: Embryologymentioning

confidence: 99%

Prenatal genetic considerations of congenital anomalies of the kidney and urinary tract (CAKUT)

2019

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Congenital anomalies of the kidney and urinary tract (CAKUT) constitute 20% of all congenital malformations occurring in one in 500 live births. Worldwide, CAKUT are responsible for 40% to 50% of pediatric and 7% of adult end‐stage renal disease. Pathogenic variants in genes causing CAKUT include monogenic diseases such as polycystic kidney disease and ciliopathies, as well as syndromes that include isolated kidney disease in conjunction with other abnormalities. Prenatal diagnosis most often occurs using ultrasonography; however, further genetic diagnosis may be made using a variety of testing strategies. Family history and pathologic examination can also provide information to improve the ability to make a prenatal diagnosis of CAKUT. Here, we provide a comprehensive overview of genetic considerations in the prenatal diagnosis of CAKUT disorders. Specifically, we discuss monogenic causes of CAKUT, associated ultrasound characteristics, and considerations for genetic diagnosis, antenatal care, and postnatal care.

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Section: Embryologymentioning

confidence: 99%

Prenatal genetic considerations of congenital anomalies of the kidney and urinary tract (CAKUT)

2019

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“…CAKUT are a spectrum of structural malformations in the kidney and/or the urinary tract which results from defects in embryonic kidney development (Capone, Morello, Taroni, & Montini, 2017). They are observed in 3-6 per 1,000 live births and represent the leading cause of end-stage renal disease in children (Hildebrandt, 2010).…”

Section: Congenital Anomalies Of the Kidney And The Urinary Tractmentioning

confidence: 99%

Cellular and molecular determinants of normal and abnormal kidney development

Tham

Smyth

2018

WIREs Developmental Biology

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Kidneys are bilateral organs required to maintain homeostasis in the body through the regulation of fluid composition and the excretion of metabolic waste products. The initial steps in organ development are characterized by cellular interactions which regulate both the position and number of kidneys formed. Once established, further development is driven by orchestrated interactions between progenitor cell populations which serve to establish both nephrons—the functional unit of the organ which filters the blood—and the complex ramified collecting duct system which transports urine to the bladder. The delicate balance involved in these processes is reflected in the emerging family of genetic or environmental factors which, when perturbed, give rise to defects in organ development or function later in life. This article is categorized under: Vertebrate Organogenesis > From a Tubular Primordium: Branched Birth Defects > Organ Anomalies

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“…Mutations in genes that control SMC differentiation are likely to contribute to the genetic complexity that underlies human congenital anomalies of the kidney and the urinary tract (CAKUT) . Identifying such genes and defining their function is important as hydroureter formation is a frequent abnormality in preterm babies which can progress to dilatation of the renal pelvis (hydronephrosis), destruction of the renal parenchyma, and culminate in end‐stage renal disease in children .…”

Section: Introductionmentioning

confidence: 99%

Delayed onset of smooth muscle cell differentiation leads to hydroureter formation in mice with conditional loss of the zinc finger transcription factor gene Gata2 in the ureteric mesenchyme

Weiss

Bohnenpoll

Kurz

et al. 2019

The Journal of Pathology

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The establishment of the peristaltic machinery of the ureter is precisely controlled to cope with the onset of urine production in the fetal kidney. Retinoic acid (RA) has been identified as a signal that maintains the mesenchymal progenitors of the contractile smooth muscle cells (SMCs), while WNTs, SHH, and BMP4 induce their differentiation. How the activity of the underlying signalling pathways is controlled in time, space, and quantity to activate coordinately the SMC programme is poorly understood. Here, we provide evidence that the Zn-finger transcription factor GATA2 is involved in this crosstalk. In mice, Gata2 is expressed in the undifferentiated ureteric mesenchyme under control of RA signalling. Conditional deletion of Gata2 by a Tbx18 cre driver results in hydroureter formation at birth, associated with a loss of differentiated SMCs. Analysis at earlier stages and in explant cultures revealed that SMC differentiation is not abrogated but delayed and that dilated ureters can partially regain peristaltic activity when relieved of urine pressure. Molecular analysis identified increased RA signalling as one factor contributing to the delay in SMC differentiation, possibly caused by reduced direct transcriptional activation of Cyp26a1, which encodes an RA-degrading enzyme. Our study identified GATA2 as a feedback inhibitor of RA signalling important for precise onset of ureteric SMC differentiation, and suggests that in a subset of cases of human congenital ureter dilatations, temporary relief of urine pressure may ameliorate the differentiation status of the SMC coat.

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Genetics of Congenital Anomalies of the Kidney and Urinary Tract: The Current State of Play

Cited by 110 publications

References 128 publications

Prenatal genetic considerations of congenital anomalies of the kidney and urinary tract (CAKUT)

Prenatal genetic considerations of congenital anomalies of the kidney and urinary tract (CAKUT)

Cellular and molecular determinants of normal and abnormal kidney development

Delayed onset of smooth muscle cell differentiation leads to hydroureter formation in mice with conditional loss of the zinc finger transcription factor gene Gata2 in the ureteric mesenchyme

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