Steroid-resistant nephrotic syndrome(SRNS)is a leading cause of pediatric end-stage renal disease.Monogenic causes have been detected in 11%-45%of pediatric SRNS using exome sequencing,1-3 leaving a large proportion o...Steroid-resistant nephrotic syndrome(SRNS)is a leading cause of pediatric end-stage renal disease.Monogenic causes have been detected in 11%-45%of pediatric SRNS using exome sequencing,1-3 leaving a large proportion of cases without a molecular diagnosis.Here,we report employing trio exome sequencing analysis to detect established and novel causes of SRNS in an international cohort of 320 unrelated families with pediatric SRNS.展开更多
Nephronophthisis-related ciliopathies(NPHP-RC)represent one of the most common causes of chronic kidney disease in the first three decades of life and are characterized by a broad genetic and clinical heterogeneity.1 ...Nephronophthisis-related ciliopathies(NPHP-RC)represent one of the most common causes of chronic kidney disease in the first three decades of life and are characterized by a broad genetic and clinical heterogeneity.1 To date,more than 90 genes have been identified that cause autosomalrecessive NPHP-RC if mutated,accounting for up to 60%of cases.1 Among these,homozygous deletions of NPHP1 are the most common cause.Ciliopathy genes localize to primary cilia,basal bodies,or the centrosome and lead to a primary ciliary disruption if mutated,thereby causing a broad phenotypical spectrum.1 Patients that suffer from NPHP-RC can either have an isolated renal phenotype,such as polyuria,polydipsia,decreased urinary concentration ability,and secondary enuresis due to loss of tubular function,or present with extrarenal symptoms including retinal degeneration,cerebellar vermis hypoplasia,or hepatic fibrosis.Patients are often diagnosed in early adolescence,reaching end-stage renal disease before 25 years of age,but early onset and rapidly progressive forms of NPHP-RC also exist.1 Renal ultrasound indicates kidneys of normal or reduced renal length with increased echogenicity and corticomedullary cysts.展开更多
基金supported by grants from the National Institutes of Health (NIH) (No.5R01DK076683-13,RC2-DK122397 to F.H.)Sequencing and data processing were performed by the Yale Centers for Mendelian Genomics funded by the National Human Genome Research Institute (No.U54 HG006504)+9 种基金supported by the Office of Faculty Development.K.Y.,C.N.F.,and N.D.M.are supported by an NIH Training Grant (No.5T32DK007726)by the 2017 Post-doctoral Fellowship Grant from the Harvard Stem Cell Institute.A.C.O.acknowledges support from the National Institutes of Health F32 Ruth L.Kirschstein Postdoctoral Individual National Research Service Award (No.DK122766)supported by a Post-Doctoral Fellowship award from the KRESCENT Program,a national kidney research training partnership of the Kidney Foundation of Canada,the Canadian Society of Nephrology,and the Canadian Institutes of Health Research.V.K.is funded by the Deutsche Forschungsgemeinschaft grant (No.403877094)supported by a Fulbright Scholar fellowship (USEFP).K.L.is funded by the Deutsche Forschungsgemeinschaft Research Foundation (No.DFG461126211)supported by the NIH (No.5K12HD052896-13,1K08DK125768-01A1)American Society of Nephrology Norman Siegel Research Scholar Grant,and Manton Center for Orphan Disease Researchsupported by the Deutsche Forschungsgemeinschaft (German Research Foundation,No.442070894)supported by a grant from the Deutsche Forschungsgemeinschaft (German Research Foundation,No.KO 6579/2-1)supported by funding from the National Institutes of Health (No.K08-DK127011)supported by the Jiang-Li Family Foundation.
文摘Steroid-resistant nephrotic syndrome(SRNS)is a leading cause of pediatric end-stage renal disease.Monogenic causes have been detected in 11%-45%of pediatric SRNS using exome sequencing,1-3 leaving a large proportion of cases without a molecular diagnosis.Here,we report employing trio exome sequencing analysis to detect established and novel causes of SRNS in an international cohort of 320 unrelated families with pediatric SRNS.
基金The Deutsche Forschungsgemeinschaft funded V.K.(No.403877094)S.Se(No.442070894)and T.J.S.(No.281319475)+1 种基金V.K.was also funded by the Else-Kroner Fresenius Stiftung(Memorial Grant)the BIH ChariteClinician Scientist Program by the Charite´e Universitatsmedizin Berlin,and the Berlin Institute of Health at Charite.S.Se.was supported by the Deutsche Forschungsgemeinschaft(German Research Foundation)lT.M.K.was also supported by a Post-Doctoral Fellowship award from the KRESCENT Program,a national kidney research training partnership of the Kidney Foundation of Canada,the Canadian Society of Nephrology,and the Canadian Institutes of Health Research.T.J.-S.received funding from the IZKF Erlangen(J70)and the Eva Luise und Horst Kohler Stiftung/Else Kroer-Fresenius Stiftung(RECORD program).
文摘Nephronophthisis-related ciliopathies(NPHP-RC)represent one of the most common causes of chronic kidney disease in the first three decades of life and are characterized by a broad genetic and clinical heterogeneity.1 To date,more than 90 genes have been identified that cause autosomalrecessive NPHP-RC if mutated,accounting for up to 60%of cases.1 Among these,homozygous deletions of NPHP1 are the most common cause.Ciliopathy genes localize to primary cilia,basal bodies,or the centrosome and lead to a primary ciliary disruption if mutated,thereby causing a broad phenotypical spectrum.1 Patients that suffer from NPHP-RC can either have an isolated renal phenotype,such as polyuria,polydipsia,decreased urinary concentration ability,and secondary enuresis due to loss of tubular function,or present with extrarenal symptoms including retinal degeneration,cerebellar vermis hypoplasia,or hepatic fibrosis.Patients are often diagnosed in early adolescence,reaching end-stage renal disease before 25 years of age,but early onset and rapidly progressive forms of NPHP-RC also exist.1 Renal ultrasound indicates kidneys of normal or reduced renal length with increased echogenicity and corticomedullary cysts.
