Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) cover a wide range of structural malformations that result from defects in the morphogenesis of the kidney and/or urinary tract. These anomalies account for about 40–50% of children with chronic kidney disease worldwide. Knowledge from genetically modified mouse models suggests that single gene mutations in renal developmental genes may lead to CAKUT in humans. However, until recently only a handful of CAKUT-causing genes were reported, most of them in familial syndromic cases. Recent findings suggest that CAKUT may arise from mutations in a multitude of different single gene causes. We focus here on single gene causes of CAKUT and their developmental origin. Currently more than 20 monogenic CAKUT-causing genes have been identified. High-throughput sequencing techniques make it likely that additional CAKUT-causing genes will be identified in the near future.

The rate of urinary tract abnormalities and the functional state of kidneys in relation to the degree of connective tissue dysplasia in children

“…РОССИЙСКИЙ ВЕСТНИК ПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 3,2016 ROSSIYSKIY VESTNIK PERINATOLOGII I PEDIATRII, 3,2016 почек аплазия одной почки встречается относитель-но часто -у 4-8%. Как правило, отсутствует левая почка.…”

“…рожденные аномалии почек и мочевыводящих путей (CAKUT) составляют 9,3-24% всех прена-тально диагностированных пороков развития, являясь причиной хронической болезни почек в 40-50% слу-чаев во всем мире [1][2][3][4]. У детей младшего возраста врожденные аномалии мочевой системы -ведущая причина хронической почечной недостаточности, трансплантации почек или диализной терапии [5].…”

Anomalías congénitas de los riñones y de las vías urinarias, una revisión de la literatura*

“…Hallazgos adicionales sugieren que hay más de 20 genes identificados involucrados en la etiología de esta patología, entre los cuales se encuentran entre otros, Ret y Gdnf que tienen a cargo la inducción de la formación de la yema ureteral, Wnt4 para la transición de mesénquima a epitelio y Agtr2 para la morfogénesis de la segmentación. La Figura 1 muestra los mecanismos del desarrollo renal y los genes causantes de CAKUT en el ratón y en humanos, al igual que otros genes candidatos a la fecha no asignados a una etapa de desarrollo renal específico 13 . Figura 1.…”

“…Mecanismos de desarrollo del riñón y correspondientes genes causantes de anomalías CAKUT en ratones y humanos. Pasos de la nefrogénesis (columna de la izquierda) y correspondientes genes causantes de CAKUT en ratones (columna central) y en humanos (columna de la derecha) 13 . …”

Diabetes-Induced Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): Nurture and Nature at Work?

“…Thus, in severe, syndromic, or familial cases, only a single gene defect (eg, in HNF1B) can cause CAKUT, whereas in sporadic cases, multiple genetic factors in combination with environmental risk factors might be underlying the disease. 21 The occurrence of incomplete penetrance in families, as well as the diverse phenotypic outcome in patients with similar gene mutations, indicates more complex disease mechanisms for CAKUT. Many key players are known to be involved in nephrogenesis and animal studies have proposed numerous candidate genes for human CAKUT, showing the heterogeneous nature of these malformations.…”