Research Topics
Genomes and Genes
| Friedhelm HildebrandtSummaryAffiliation: University of Michigan Country: USA Publications
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Detail Information
Publications
Exome sequencing reveals cubilin mutation as a single-gene cause of proteinuriaBugsu Ovunc
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA
J Am Soc Nephrol 22:1815-20. 2011..In summary, we report successful use of exome capture and massively parallel re-sequencing to identify a rare, single-gene cause of nephropathy...- 3D spheroid defects in NPHP knockdown cells are rescued by the somatostatin receptor agonist octreotideAmiya K Ghosh
Department of Pediatrics, University of Michigan Health System, 1150 West Medical Center Dr, Ann Arbor, MI 48109 5646, USA
Am J Physiol Renal Physiol 303:F1225-9. 2012..This study reveals that the loss of Nphp3, Nphp6, or Nphp8 leads to cilia abnormalities and cell polarity defects, resulting in spheroid abnormalities, which can be rescued by inhibiting cAMP levels with octreotide treatment... - Nephronophthisis: disease mechanisms of a ciliopathyFriedhelm Hildebrandt
Department of Pediatrics, Howard Hughes Medical Institute, University of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109 5646, USA
J Am Soc Nephrol 20:23-35. 2009..Nephrocystins are highly conserved in evolution, thereby allowing the use of animal models to develop future therapeutic approaches... 
Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease?Friedhelm Hildebrandt
Department of Pediatrics, University of Michigan, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109 0646, USA
Nat Rev Genet 6:928-40. 2005..Protein-protein interactions among cystoproteins, and their strong evolutionary conservation, provide a basis for a multidisciplinary approach to unravelling the novel signalling mechanisms that are involved in this disease group...
Specific podocin mutations determine age of onset of nephrotic syndrome all the way into adult lifeFriedhelm Hildebrandt
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
Kidney Int 75:669-71. 2009....- Nephronophthisis-associated ciliopathiesFriedhelm Hildebrandt
Department of Pediatrics, University of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109 0646, USA
J Am Soc Nephrol 18:1855-71. 2007..Positional cloning of additional causative genes of NPHP will elucidate further signaling mechanisms that are involved, thereby establishing therapeutic approaches using animal models in mouse, zebrafish, and Caenorhabditis elegans... - Genetic kidney diseasesFriedhelm Hildebrandt
Howard Hughes Medical Institute and Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
Lancet 375:1287-95. 2010.... - Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategyEdgar A Otto
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
J Med Genet 48:105-16. 2011..To overcome the broad genetic locus heterogeneity, a strategy of DNA pooling with consecutive massively parallel resequencing (MPR) was devised... - Mutation analysis in nephronophthisis using a combined approach of homozygosity mapping, CEL I endonuclease cleavage, and direct sequencingEdgar A Otto
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
Hum Mutat 29:418-26. 2008..3812+2T>C and p.R1259X), and in NPHP4 (p.R59X, p.T1004fs, and p.V1091fs). The combined homozygosity mapping and CEL I endonuclease mutation analysis approach allowed us to identify rare mutations in a large cohort of patients at low cost... - CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290Nicholas T Gorden
Division of Genetics and Developmental Medicine, Department of Pediatrics, School of Medicine, University of Washington, Seattle, WA 98195, USA
Am J Hum Genet 83:559-71. 2008..These observations extend the genetic spectrum of JSRD and provide a model system for studying extragenic modifiers in JSRD and other ciliopathies... - Nephrotic syndrome in the first year of life: two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2)Bernward G Hinkes
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
Pediatrics 119:e907-19. 2007..Therefore, we analyzed all 4 of the genes jointly in a large European cohort of 89 children from 80 families with nephrotic syndrome manifesting in the first year of life and characterized genotype/phenotype correlations... - Genotype/phenotype correlation in nephrotic syndrome caused by WT1 mutationsGil Chernin
Departments of Pediatrics, University of Michigan Health System, Ann Arbor, MI 48109 5646, USA
Clin J Am Soc Nephrol 5:1655-62. 2010..Here, the genotype/phenotype correlation regarding the outcome and risk for WT in 52 patients from 51 families with NS due to WT1 mutations is described... - Nephrocystin-3 is required for ciliary function in zebrafish embryosWeibin Zhou
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
Am J Physiol Renal Physiol 299:F55-62. 2010..Thus nphp3, cooperating with nphp2/inversin, plays an essential role related to ciliary function, and the knockdown provides an animal model that may be used for studies of the pathogenesis and therapy for this disease... - Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndromeSaskia F Heeringa
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109 5646, USA
Nephrol Dial Transplant 23:3527-33. 2008..So far, more than 80 different mutations of NPHS1 causing CNF have been published... - Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS)Rasheed Gbadegesin
Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Nephrol Dial Transplant 23:1291-7. 2008..Mutations in two other genes WT1 and LAMB2 may also cause IDMS. We therefore determine in this study the relative frequency of mutations in PLCE1, WT1 or LAMB2 as the cause of IDMS in a worldwide cohort... - Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndromeBernward Hinkes
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA
J Am Soc Nephrol 19:365-71. 2008..Because the age of onset can vary by several years among those with identical mutations, additional factors may modify the phenotype... - A systematic approach to mapping recessive disease genes in individuals from outbred populationsFriedhelm Hildebrandt
Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America
PLoS Genet 5:e1000353. 2009.... - COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafnessSaskia F Heeringa
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
J Clin Invest 121:2013-24. 2011..These data suggest that coenzyme Q10-related forms of SRNS and hearing loss can be molecularly identified and potentially treated... - Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathyEdgar A Otto
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA
Nat Genet 42:840-50. 2010..This work identifies loss of SDCCAG8 function as a cause of a retinal-renal ciliopathy and validates exome capture analysis for broadly heterogeneous single-gene disorders... - Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulinEdgar A Otto
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA
Nat Genet 37:282-8. 2005..Our studies emphasize the central role of ciliary dysfunction in the pathogenesis of SLSN... - Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathyJOHN F O'TOOLE
Department of Pediatrics, University of Michigan, Ann Arbor, 48109 5646, USA
J Clin Invest 120:791-802. 2010..Our data highlight an emerging link between mitochondria and ciliary dysfunction, and suggest that further understanding the enzymatic activity and substrates of XPNPEP3 will illuminate novel cystogenic pathways... - Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS)Dominik S Schoeb
Department of Pediatrics, University of Michigan, 1150 W Medical Center Drive Drive, Ann Arbor, MI, USA
Nephrol Dial Transplant 25:2970-6. 2010..CNS is defined as steroid-resistant nephrotic syndrome (SRNS) within the first 90 days of life. Currently, more than 119 different mutations of NPHS1 have been published affecting most exons... - Adequate use of allele frequencies in Hispanics--a problem elucidated in nephrotic syndromeGil Chernin
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
Pediatr Nephrol 25:261-6. 2010..Future larger studies may employ a total genome search for linkage to test self-identified Hispanic ethnicity for true Mesoamerican versus Caucasian ethnicity in order to generate valid genetic data... - Mutation analysis of NPHS1 in a worldwide cohort of congenital nephrotic syndrome patientsBugsu Ovunc
Department of Pediatrics and Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
Nephron Clin Pract 120:c139-46. 2012..Mutations in the NPHS1 gene encoding nephrin, are a major cause for CNS. Currently, more than 173 different mutations of NPHS1 have been published as causing CNS, affecting most exons... - Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signalingMoumita Chaki
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109, USA
Cell 150:533-48. 2012..Our findings link degenerative diseases of the kidney and retina, disorders of increasing prevalence, to mechanisms of DDR... - Mutational analysis of NPHS2 and WT1 in frequently relapsing and steroid-dependent nephrotic syndromeRasheed Gbadegesin
Department of Pediatrics, Division of Nephrology, Ann Arbor, MI 48109, USA
Pediatr Nephrol 22:509-13. 2007..0 in SRNS patients; p < 0.001). No NPHS2 or WT1 mutations were found in patients with FRNS/SDNS and uncomplicated SSNS. The hypothesis that FRNS/SDNS may be associated with heterozygous mutations in NPHS2 or WT1 was not confirmed... - Mutational analysis in 119 families with nephronophthisisEdgar A Otto
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109 0676, USA
Pediatr Nephrol 22:366-70. 2007..No mutations in known NPHP genes or in the candidate genes, BCL2 and CYS1, were found sufficient to explain NPHP in affected individuals. These findings demonstrate the need to evaluate additional candidate genes as the cause of NPHP... - Medullary cystic kidney disease type 1: mutational analysis in 37 genes based on haplotype sharingMatthias T F Wolf
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109-0646, USA, and University Children's Hospital, Freiburg University, Germany
Hum Genet 119:649-58. 2006..This may point to involvement of different genes within the MCKD1 critical region... - Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndromeGil Chernin
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
Pediatr Nephrol 23:1455-60. 2008..Knowledge of mutation rate of NPHS2 in different populations of SRNS patients facilitates the physician in planning a suitable genetic screening strategy for patients... - Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to chromosome 9q33.2-q34.2 by total genome search for linkageMatthias T F Wolf
Department of Pediatrics and Communicable Diseases, University of Michigan, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0646, USA
Nephrol Dial Transplant 20:909-14. 2005..It is localized on chromosome 9q33.2-q34.2. The identification of the responsible gene will provide new insights into the molecular basis of nephrolithiasis... - Identification of two novel CAKUT-causing genes by massively parallel exon resequencing of candidate genes in patients with unilateral renal agenesisPawaree Saisawat
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
Kidney Int 81:196-200. 2012..Thus, heterozygous missense mutations in FRAS1 and FREM2 cause non-syndromic CAKUT in humans... - Pseudodominant inheritance of nephronophthisis caused by a homozygous NPHP1 deletionJulia Hoefele
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109 5646, USA
Pediatr Nephrol 26:967-71. 2011..Furthermore, three out of four patients developed ESRD between 27 and 43 years of age, which may be influenced by yet unknown modifier genes... - Identification of the first gene locus (SSNS1) for steroid-sensitive nephrotic syndrome on chromosome 2pRainer G Ruf
Department of Pediatrics, University of Michigan Health System, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0646, USA
J Am Soc Nephrol 14:1897-900. 2003..01 at D2S145). The first gene locus for SSNS, as a first step to detect the responsible gene, was thus identified. There was clear evidence for genetic locus heterogeneity upon examination of ten additional families with SSNS... - Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determinationEdgar A Otto
Department of Pediatrics, 8220C MSRB III, 1150 West Medical Center Drive, University of Michigan, Ann Arbor, Michigan 48109, USA
Nat Genet 34:413-20. 2003..The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination... - Mapping of a new locus for congenital anomalies of the kidney and urinary tract on chromosome 8q24Shazia Ashraf
1Department of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, USA
Nephrol Dial Transplant 25:1496-501. 2010..Previous studies have mapped autosomal dominant loci for CAKUT. We here report a genome-wide search for linkage in a large pedigree of Somalian descent containing eight affected individuals with a non-syndromic form of CAKUT... - Mutational analysis of the NPHP4 gene in 250 patients with nephronophthisisJulia Hoefele
Department of Pediatrics, Human Genetics, University of Michigan, Ann Arbor, Michigan, USA
Hum Mutat 25:411. 2005.... - Evidence of oligogenic inheritance in nephronophthisisJulia Hoefele
Departments of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
J Am Soc Nephrol 18:2789-95. 2007..Our findings suggest that oligogenicity may occur in cases of nephronophthisis... - Mutation analysis in Bardet-Biedl syndrome by DNA pooling and massively parallel resequencing in 105 individualsSabine Janssen
Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, MI 48109 5446, USA
Hum Genet 129:79-90. 2011..Thus, DNA pooling combined with MPR offers a valuable strategy for mutation analysis of large patient cohorts, especially in genetically heterogeneous diseases such as BBS... - Molecular cloning and expression of phospholipase C epsilon 1 in zebrafishWeibin Zhou
Departments of Pediatrics and Human Genetics, University of Michigan, 8220 MSRB3, 1150 W Medical Center Drive, Ann Arbor, MI 48109 5646, USA
Gene Expr Patterns 9:282-8. 2009..Our results suggest that zebrafish may be used as a model organism to address the function of PLCepsilon during the development of these organs... - Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversibleBernward Hinkes
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA
Nat Genet 38:1397-405. 2006..These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotic syndrome... - No evidence for genotype/phenotype correlation in NPHS1 and NPHS2 mutationsMichael Schultheiss
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
Pediatr Nephrol 19:1340-8. 2004..We report ten novel mutations in the nephrin gene. Our data do not suggest any genotype/phenotype correlation in the 5 patients with mutations in both the NPHS1 and the NPHS2 genes... - Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndromeRainer G Ruf
Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, Michigan, USA
Kidney Int 66:564-70. 2004..Sporadic mutations in the Wilms' tumor suppressor gene WT1 have been found to be present in patients with SRNS in association with Wilms' tumor (WT) and urinary or genital malformations, as well as in patients with isolated SRNS... - Mutations in the Wilms' tumor 1 gene cause isolated steroid resistant nephrotic syndrome and occur in exons 8 and 9Bettina Mucha
Department of Pediatrics, University of Michigan, Ann Arbor, 48109, USA
Pediatr Res 59:325-31. 2006..Kidney Int 66: 564-570, 2004) indicate that screening of WT1 exons 8 and 9 in patients with sporadic SRNS is sufficient to detect pathogenic WT1 mutations and may open inroads into differential therapy of SRNS... - Retinitis pigmentosa and renal failure in a patient with mutations in INVSJOHN F O'TOOLE
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109 0676, USA
Nephrol Dial Transplant 21:1989-91. 2006..The NPHP type 2 is distinguished from other types of NPHP by its early age of onset and by cystic enlargement of the kidneys... - Genotype-phenotype correlation in 440 patients with NPHP-related ciliopathiesMoumita Chaki
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
Kidney Int 80:1239-45. 2011..We also found nine novel mutations in the NPHP genes. Thus, our studies have important implications for genetic counseling and planning of renal replacement therapy... - CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the ciliumJi Eun Lee
Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California, USA
Nat Genet 44:193-9. 2012..Our data identify CEP41 mutations as a cause of JBTS and implicate tubulin post-translational modification in the pathogenesis of human ciliary dysfunction... - Characterization of mesonephric development and regeneration using transgenic zebrafishWeibin Zhou
Univ of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Dr, Ann Arbor, MI 48109 5646, USA
Am J Physiol Renal Physiol 299:F1040-7. 2010..This suggests that wt1b may serve as an early marker of fated renal progenitor cells. The synchronous nature of regenerative neonephrogenesis suggests that this process may be useful for studies of nephron development... - Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndromeRainer G Ruf
Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
J Am Soc Nephrol 15:722-32. 2004.... - Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndromeBethan E Hoskins
Department of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, MI, USA
Am J Hum Genet 80:800-4. 2007..We thereby identified heterozygous mutations in SIX5 as a novel cause of BOR... - Telomeric refinement of the MCKD1 locus on chromosome 1q21Matthias T F Wolf
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109-0646, USA
Kidney Int 66:580-5. 2004..CONCLUSION: We confirm the MCKD1 locus on chromosome 1q21 and show further refinement of the MCKD1 locus to 2.1 Mb. This allowed us to exclude another 17 genes as positional candidate genes... - Mutation analysis of the Uromodulin gene in 96 individuals with urinary tract anomalies (CAKUT)Matthias T F Wolf
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
Pediatr Nephrol 24:55-60. 2009..Six previously known and seven new single nucleotide polymorphisms (SNPs) were detected. As no UMOD mutations were identified in these 96 patients with CAKUT, UMOD mutations do not seem to be a significant cause of CAKUT in this cohort... - The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4John A Sayer
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA
Nat Genet 38:674-81. 2006..Our findings help establish the link between centrosome function, tissue architecture and transcriptional control in the pathogenesis of cystic kidney disease, retinal degeneration, and central nervous system development... - The retinitis pigmentosa protein RP2 interacts with polycystin 2 and regulates cilia-mediated vertebrate developmentToby Hurd
Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA
Hum Mol Genet 19:4330-44. 2010..This work suggests that RP2 may be an important regulator of ciliary function through its association with polycystin 2 and provides evidence of a further link between retinal and renal cilia function... - Inducible podocyte injury and proteinuria in transgenic zebrafishWeibin Zhou
University of Michigan Medical School, 8240 MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109 5646, USA
J Am Soc Nephrol 23:1039-47. 2012..These data support the use of these transgenic zebrafish as a model system for studies of glomerular pathogenesis and podocyte regeneration... - Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosisMassimo Attanasio
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA
Nat Genet 39:1018-24. 2007..Thus, we identify Glis2 as a transcription factor mutated in NPHP and demonstrate its essential role for the maintenance of renal tissue architecture through prevention of apoptosis and fibrosis... - Interaction of ciliary disease protein retinitis pigmentosa GTPase regulator with nephronophthisis-associated proteins in mammalian retinasCarlos A Murga-Zamalloa
Department of Ophthalmology and Visual Sciences, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA
Mol Vis 16:1373-81. 2010..Perturbations in the assembly of RPGR complexes are associated with retinal degeneration. This study was undertaken to delineate the composition and dissection of RPGR complexes in mammalian retinas... - Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndromeBoris Utsch
Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, USA
Pediatr Nephrol 21:32-5. 2006..One patient had the association of JBTS and NPHP with chronic renal failure. This is the first report of AHI1 mutations causing JBTS associated with NPHP, confirming the clinical and genetic heterogeneity of NPHP... - Identification of BRAF as a new interactor of PLCepsilon1, the protein mutated in nephrotic syndrome type 3Hassan Chaib
Department of Pediatrics, University of Michigan Drive, Ann Arbor, MI 48109 5646, USA
Am J Physiol Renal Physiol 294:F93-9. 2008..By immunohistochemistry in rat kidney, we demonstrate that both proteins are coexpressed and colocalize in developing and mature glomerular podocytes, reporting for the first time the expression of BRAF in the glomerular podocyte... - Mutations of the Uromodulin gene in MCKD type 2 patients cluster in exon 4, which encodes three EGF-like domainsMatthias T F Wolf
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109, USA
Kidney Int 64:1580-7. 2003..In contrast, recently, another group described mutations in the UMOD gene as responsible for MCKD2 and familial juvenile hyperuricemic nephropathy (FJHN)... - SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexesRainer G Ruf
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA
Proc Natl Acad Sci U S A 101:8090-5. 2004..Identification of SIX1 mutations as causing BOR/BO offers insights into the molecular basis of otic and renal developmental diseases in humans... - Clinical and histological presentation of 3 siblings with mutations in the NPHP4 geneJulia Hoefele
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
Am J Kidney Dis 43:358-64. 2004..Progression to end-stage renal disease occurred between the ages of 17 and 22 years. None of the renal transplants showed recurrence of the disease. Retinitis pigmentosa was absent in all affected family members... - Expression and phenotype analysis of the nephrocystin-1 and nephrocystin-4 homologs in Caenorhabditis elegansMatthias T F Wolf
Department of Pediatrics and Communicable Diseases, University of Michigan, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109 0646, USA
J Am Soc Nephrol 16:676-87. 2005..The NPHP homologs may be necessary for initial assembly of the cilium, whereas the polycystic kidney disease homologs may function as sensory transducers... - A novel TRPC6 mutation that causes childhood FSGSSaskia F Heeringa
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, United States of America
PLoS ONE 4:e7771. 2009..Until today, seven different mutations in TRPC6 have been identified as a cause of autosomal-dominant focal segmental glomerulosclerosis (FSGS) in adults... - NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisisEdgar A Otto
University of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109 5646, USA
J Am Soc Nephrol 19:587-92. 2008..Our genetic and functional data support the assumption that mutations in NEK8 cause nephronophthisis (NPHP9), adding another link between proteins mutated in cystic kidney disease and their localization to cilia and centrosomes... - A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathiesHemant Khanna
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA
Nat Genet 41:739-45. 2009..Our data represent an example of modification of a discrete phenotype of syndromic disease and highlight the importance of a multifaceted approach for the discovery of modifier alleles of intermediate frequency and effect... - A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolutionEdgar Otto
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
Am J Hum Genet 71:1161-7. 2002..In addition, we demonstrate two loss-of-function mutations of NPHP4 in patients from two families with SLS. Thus, we have identified a novel gene with critical roles in renal tissue architecture and ophthalmic function... - Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndromeVincent Cantagrel
Department of Neurosciences, Laboratory of Neurogenetics, Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0691, USA
Am J Hum Genet 83:170-9. 2008..Overexpression of human wild-type but not patient mutant ARL13B rescued the Arl13b scorpion zebrafish mutant. Thus, ARL13B has an evolutionarily conserved role mediating cilia function in multiple organs... - Multiple urinary tract malformations with likely recessive inheritance in a large Somalian kindredAndreas Pasch
University of Michigan, Department of Pediatrics, Ann Arbor, MI 48109-0640, USA
Nephrol Dial Transplant 19:3172-5. 2004 - A gene locus for steroid-resistant nephrotic syndrome with deafness maps to chromosome 14q24.2Rainer G Ruf
Department of Pediatrics, University of Michigan, Ann Arbor, 48109, USA
J Am Soc Nephrol 14:1519-22. 2003..Lack of homozygosity defined D14S1065 and D14S273 as flanking markers to a 10.7 cM interval. The identification of the responsible gene will provide new insights into the molecular basis of nephrotic syndrome and sensorineural deafness... - AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisisCarrie M Louie
Howard Hughes Medical Institute, Department of Pediatrics, University of California, San Diego, La Jolla, USA
Nat Genet 42:175-80. 2010..Our data support context-specific roles for AHI1 as a contributor to retinopathy and show that AHI1 may explain a proportion of the variability in retinal phenotypes observed in nephronophthisis... - Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosisHeike Olbrich
Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, 79106 Freiburg, Germany
Nat Genet 34:455-9. 2003..Interventional studies in the pcy mouse have shown beneficial effects by modification of protein intake and administration of methylprednisolone, suggesting therapeutic strategies for treating individuals with NPHP3... - Nephrocystin-1 interacts directly with Ack1 and is expressed in human collecting ductLorraine Eley
Institute of Human Genetics, International Centre for Life, University of Newcastle upon Tyne, NE1 3BZ, UK
Biochem Biophys Res Commun 371:877-82. 2008..These data define Ack1 as a novel interaction partner of nephrocystin-1 and implicate cell-cell junctions and the renal collecting duct in the pathology of nephronophthisis... - Haplotype analysis improves molecular diagnostics of autosomal recessive polycystic kidney diseaseMark B Consugar
Division of Nephrology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Am J Kidney Dis 45:77-87. 2005..The common mutation, T36M, was found to have a single European origin, about 1,225 years ago. CONCLUSION: Improved haplotype analysis of ARPKD complements mutation-based diagnostics and helps trace the history of common PKHD1 mutations... - Confirmation of the ATP6B1 gene as responsible for distal renal tubular acidosisRainer Ruf
University Children s Hospital, Mathildenstrasse 1, 79106 Freiburg, Germany
Pediatr Nephrol 18:105-9. 2003..Therefore, we conducted mutational analysis in 15 families and identified potential loss-of-function mutations in ATP6B1in 8. We thus confirmed that defects in this gene are responsible for recessive dRTA with sensorineural deafness... - Mutation analysis of NPHP6/CEP290 in patients with Joubert syndrome and Senior-Løken syndromeJuliana Helou
J Med Genet 44:657-63. 2007.... - The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndromeMarion Delous
Institut National de la Santé et de la Recherche Médicale INSERM U 574, Hopital Necker Enfants Malades, 75015 Paris, France
Nat Genet 39:875-81. 2007..Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder... - Identification of a gene locus for Senior-Løken syndrome in the region of the nephronophthisis type 3 geneHeymut Omran
University Children s Hospital Freiburg, University of Bonn, Bonn, Germany
J Am Soc Nephrol 13:75-9. 2002..Localization of a SLS locus to the region of NPHP3 opens the possibilities of both diseases arising by mutations within the same pleiotropic gene or two adjacent genes... - Identification of the human CYS1 gene and candidate gene analysis in Boichis diseaseManfred Fliegauf
Department of Pediatrics and Adolescent Medicine, University of Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany
Pediatr Nephrol 18:498-505. 2003..All three coding exons were amplified by polymerase chain reaction and directly sequenced. Despite the failure to detect a mutation, the human cystin gene remains an interesting candidate for recessive cystic kidney disease... - Recessive NPHS2 (Podocin) mutations are rare in adult-onset idiopathic focal segmental glomerulosclerosisNing He
Division of Nephrology, Toronto General Hospital, University Health Network and University of Toronto, Toronto, Ontario, Canada
Clin J Am Soc Nephrol 2:31-7. 2007..These data do not support R229Q as a disease-causing mutation for steroid-resistant FSGS... - In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouseBo Chang
The Jackson Laboratory, Bar Harbor, ME 04609, USA
Hum Mol Genet 15:1847-57. 2006..Our findings suggest a critical function for CEP290 in ciliary transport and provide insights into the mechanism of early-onset photoreceptor degeneration... - Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetryHeike Olbrich
Department of Pediatrics and Adolescent Medicine, Albert Ludwigs University, 79106 Freiburg, Germany
Nat Genet 30:143-4. 2002..Here we characterize the full-length 14-kb transcript of DNAH5. Sequence analysis in individuals with PCD with randomization of LR asymmetry identified mutations resulting in non-functional DNAH5 proteins...
Research Grants
- Identification and function of new genes causing childhood nephrotic syndromeFriedhelm Hildebrandt; Fiscal Year: 2007....
- Identification of new genes causing nephronophthisisFriedhelm Hildebrandt; Fiscal Year: 2007..abstract_text> ..
- Function of NPHP6 a novel gene for Senior-Loken syndromeFriedhelm Hildebrandt; Fiscal Year: 2009..Identification of NPHP6 as a new cause of NPHP and SLS opens new inroads into the understanding of disease mechanisms of renal cystic disease and retinitis pigmentosa. ..
- Identifying new genes for branchio-oto-renal syndromeFriedhelm Hildebrandt; Fiscal Year: 2009..Identification of new genes causing branchio-oto-renal syndrome will offer new insights into the pathomechanisms of hearing defects, urinary tract malformations as well as kidney and ear development. ..
- Novel genetics, pathobiology, and therapy of nephronophthisis-related ciliopathieFriedhelm Hildebrandt; Fiscal Year: 2010..It will allow development of animal models and novel therapeutic approaches to these degenerative diseases. ..
- Identification and function of new genes causing childhood nephrotic syndromeFriedhelm Hildebrandt; Fiscal Year: 2010....
- Functional characterization of the gene NPHP4Friedhelm Hildebrandt; Fiscal Year: 2007..abstract_text> ..
- Function of NPHP6 a novel gene for Senior-Loken syndromeFriedhelm Hildebrandt; Fiscal Year: 2007..Identification of NPHP6 as a new cause of NPHP and SLS opens new inroads into the understanding of disease mechanisms of renal cystic disease and retinitis pigmentosa. ..
- New genes and pathomechanisms of congenital abnormalities of the kidney (CAKUT)Friedhelm Hildebrandt; Fiscal Year: 2010....