Impact of next generation sequencing on our understanding of CAKUT

Nigam, Anukrati; Knoers, Nine V A M; Renkema, Kirsten Y.

doi:10.1016/j.semcdb.2018.08.013

Cited by 21 publications

(17 citation statements)

References 105 publications

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“…Congenital anomalies of the kidney and urinary tract (CAKUT), the incidence of which is around 0.2% by prenatal sonography, have been reported to accounts for 40%-50% of the global pediatric end-stage renal disease (ESRD) as well as 7% of global adult ESRD. 1 Accumulating evidences from animal and human studies suggest that genetic factors contribute to CAKUT. 2 To date, more than 200 clinical syndromes were described phenotypes of CAKUT, 3 and approximately 40 monogenic genes were identified to cause renal and urinary abnormality if mutated, which explained 5%-20% of CAKUT cases.…”

Section: Introductionmentioning

confidence: 99%

“…Congenital anomalies of the kidney and urinary tract (CAKUT), the incidence of which is around 0.2% by prenatal sonography, have been reported to accounts for 40%‐50% of the global pediatric end‐stage renal disease (ESRD) as well as 7% of global adult ESRD 1 . Accumulating evidences from animal and human studies suggest that genetic factors contribute to CAKUT 2 .…”

Section: Introductionmentioning

confidence: 99%

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Molecular diagnostic in fetuses with isolated congenital anomalies of the kidney and urinary tract by whole‐exome sequencing

Zhou

Yan

Shao

et al. 2020

Clinical Laboratory Analysis

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular diagnostic in fetuses with isolated congenital anomalies of the kidney and urinary tract by whole‐exome sequencing

Zhou

Yan

Shao

et al. 2020

Clinical Laboratory Analysis

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“…The benefit for genetics and diagnosis of congenital kidney anomalies is also obvious. However, the majority of human CAKUT cases are idiopathic, and their causes remain unknown despite the strong familiar aggregation in approximated 15% of patients (91,280). In addition to genetic causes, environmental and epigenetic factors are also involved, while only approximately 5-20% of CAKUT are considered monogenic disease (281)(282)(283).…”

Section: Discussionmentioning

confidence: 99%

“…Sequencing of human CAKUT samples has confirmed that several genes identified as essential regulators of early kidney induction in mice are also mutated in human patients (91). As in mice, mutations in transcription factors HOX11 (92), PAX8 (93), SALL1 (94), WT1 (95), as well as in signaling pathways such as FGFR1 (96) (syndromic; renal agenesis in Kallman syndrome), FGF20 (79) GREM1 (97), and RET (94, 98), cause renal aplasia in humans.…”

Section: Mutations Identified In Human Renal Aplasiamentioning

confidence: 98%

Mouse Models of Congenital Kidney Anomalies

Kuure

Sariola

2020

Advances in Experimental Medicine and Biology

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Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects, which cause the majority of chronic kidney diseases in children. CAKUT covers a wide range of malformations that derive from deficiencies in embryonic kidney and lower urinary tract development, including renal aplasia, hypodysplasia, hypoplasia, ectopia, and different forms of ureter abnormalities. The majority of the genetic causes of CAKUT remain unknown. Research on mutant mice has identified multiple genes that critically regulate renal differentiation. The data generated from this research have served as an excellent resource to identify the genetic bases of human kidney defects and have led to significantly improved diagnostics. Furthermore, genetic data from human CAKUT studies have also revealed novel genes regulating kidney differentiation.

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“…[5][6][7][8][9][10][11][12][13][14][15][16].6% of patients with CAKUT carry pathogenic CNV(9,10,22,23, 36,(49)(50)(51) which targeted panel cannot detect. It is likely that CNVs in gene(s) or mutations in the noncoding regions not targeted by our customized panel could be responsible for the disease in the cohort.…”

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confidence: 99%

Deciphering the Mutation Spectrum in South Indian Children With Congenital Anomalies of the Kidney and Urinary Tract

Narikot

Pardeshi

et al. 2021

Preprint

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Background: Congenital anomalies of the kidney and urinary tract (CAKUT) cover a spectrum of structural malformations that result from aberrant morphogenesis of kidney and urinary tract. It is the most prevalent cause of kidney failure in children. Hence, it is important from a clinical perspective to unravel the molecular etiology of kidney and urinary tract malformations. Causal variants in genes that direct various stages of development of kidney and urinary tract in fetal life have been identified in 5–20 % of CAKUT patients from Western countries. Recent advances in next generation sequencing technology and decreasing cost offer the opportunity to characterize the genetic burden of CAKUT in Indian population and facilitate integration of genetic diagnostics in care of children with CAKUT. Methods: Customized targeted panel sequencing was performed to identify mutations in 31 genes known to cause human CAKUT in 69 south Indian children with CAKUT. The NGS data was filtered using standardized pipeline and the variants were classified using ACMG criteria. Genotype and phenotype correlations were performed. Results: The cohort consisted of children mostly with posterior urethral valve (PUV) (39.1%), vesico-ureteric reflux (VUR) (33.3%) and multi-cystic dysplastic kidney (MCDK) (7.2%). Likely pathogenic variants were identified in two genes (TNXB and CHD1L) in 2 children (9 %) with CAKUT. One child diagnosed with posterior urethral valve (PUV) had mutation in two different genes [TNXB (p. Gln286fs), and CHD1L (p. Ser837fs)], while second child with left duplex system had a single gene mutation in TNXB gene (p. Gln286fs). Conclusions: The present study identified novel monogenic mutations in only a small proportion of patients with CAKUT using a targeted gene panel. The low prevalence of genetic cause may be due to higher proportion of children with abnormalities in lower urinary tract than hypodysplasia of kidneys. Clinical or whole exome sequencing may be a better method to characterize the genetic profile of Indians patients with CAKUT.

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Impact of next generation sequencing on our understanding of CAKUT

Cited by 21 publications

References 105 publications

Molecular diagnostic in fetuses with isolated congenital anomalies of the kidney and urinary tract by whole‐exome sequencing

Molecular diagnostic in fetuses with isolated congenital anomalies of the kidney and urinary tract by whole‐exome sequencing

Mouse Models of Congenital Kidney Anomalies

Deciphering the Mutation Spectrum in South Indian Children With Congenital Anomalies of the Kidney and Urinary Tract

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