The Experts below are selected from a list of 291714 Experts worldwide ranked by ideXlab platform
Hae Il Cheong - One of the best experts on this subject based on the ideXlab platform.
-
muscle involvement in Dent disease 2
Pediatric Nephrology, 2014Co-Authors: Eujin Park, Il Soo Ha, Yoo Mee Choi, Hee Gyung Kang, Se Jin Park, Hae Il Cheong, Yonghoon Park, Hyun Jin ChoiAbstract:Background Dent disease, an X-linked recessive renal tubulopathy, is caused by mutations in either CLCN5 (Dent disease 1) or OCRL (Dent disease 2). OCRL mutations can also cause Lowe syndrome. In some cases it is difficult to differentiate Dent disease 1 and 2 on the basis of clinical features only without genetic tests. Several studies have shown differences in serum levels of muscle enzymes between these diseases. The aim of our study was to test the validity of these findings.
-
Dent 2 disease a mild variant of lowe syndrome
The Journal of Pediatrics, 2009Co-Authors: Arend Bokenkamp, Robert J Unwin, Hae Il Cheong, Velibor Tasic, Detlef Bockenhauer, Bernd Hoppe, Michael LudwigAbstract:Objective To compare the renal and extra-renal phenotypes of patients classified as having Dent disease, Dent-2 disease, or Lowe syndrome. Study design Chart review of data from 93 patients with iDentified voltage-gated chloride channel and chloride/proton antiporter 5 gene and oculo-cerebro-renal syndrome of Lowe gene mutations observed by the authors, complemented with published data. Results There was a wide overlap of renal symptoms. Nephrocalcinosis was more prevalent in Dent-1 disease, and renal tubular acidosis, aminoaciduria, and renal failure was more prevalent in patients with Lowe syndrome. Patients with Lowe syndrome were shorter than patients with Dent-1 disease, and patients with Dent-2 disease showed an intermediate phenotype. Three patients with Dent-2 disease had mild peripheral cataract, and 9 patients were noted to have some degree of mental retardation. Conclusion There is a phenotypic continuum within patients with Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for loss of oculo-cerebro-renal syndrome of Lowe gene function.
-
Renal manifestations of Dent disease and Lowe syndrome
Pediatric Nephrology, 2008Co-Authors: Hyun Jin Choi, Il Soo Ha, Yong Choi, Hae Il CheongAbstract:To date, two responsible genes for the development of Dent disease have been iDentified: CLCN5 and OCRL1 . In this study, genotype-phenotype correlations were studied in patients with Dent disease and those with Lowe syndrome. Among the 12 boys with a phenotype typical of Dent disease, nine had a mutation in CLCN5 (Dent disease 1), two had a mutation in OCRL1 (Dent disease 2), and one had no mutations in either gene. All seven boys with a clinical diagnosis of Lowe syndrome had a mutation in OCRL1 . Patients with Lowe syndrome showed more frequent hypophosphatemia/rickets and more prominent tubular proteinuria than patients with Dent disease 1, and patients with Dent disease 2 had higher degree of tubular proteinuria and hypercalciuria than patients with Dent disease 1. Additionally, one patient with Dent disease 2 showed a mild degree of developmental delay, elevated serum muscle enzyme levels, and cryptorchidism. In this study, the genetic heterogeneity in Dent disease and the phenotypic heterogeneity in Lowe syndrome were confirmed. In patients with Dent disease, the presence of the above-mentioned extrarenal manifestations indicates that it is more likely that the patient is affected by Dent disease 2 than by Dent disease 1.
Takashi Sekine - One of the best experts on this subject based on the ideXlab platform.
-
japanese Dent disease has a wider clinical spectrum than Dent disease in europe usa genetic and clinical studies of 86 unrelated patients with low molecular weight proteinuria
Nephrology Dialysis Transplantation, 2014Co-Authors: Fusako Komoda, Mitsunobu Shimadzu, Takeshi Matsuyama, Kenichiro Miura, Akira Ashida, Junko Takita, Takashi Sekine, Takashi IgarashiAbstract:Dent disease is an X-linked disorder characterized by low-molecular-weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, urolithiasis and renal dysfunction. Dent disease is caused by mutations in at least two genes, i.e. CLCN5 and OCRL1, and its genetic background and phenotypes are common among European countries and the USA. However, only few studies on Dent disease in Japan, which was originally called 'low-molecular-weight proteinuric disease', have been reported thus far. In this study, we analysed genetic background and clinical phenotype and laboratory data of 86 unrelated Japanese Dent disease patients. The results demonstrated that the genetic basis of Japanese Dent disease was nearly iDentical to those of Dent disease in other countries. Of 86 unrelated Japanese Dent patients, 61 possessed mutations in CLCN5 (Dent-1), of which 27 were novel mutations; 11 showed mutations in OCRL1 (Dent-2), six of which were novel, and the remaining 14 patients showed no mutations in CLCN5 or OCRL1 (Dent-NI). Despite the similarity in genetic background, hypercalciuria was detected in only 51%, rickets in 2% and nephrocalcinosis in 35%. Although the patients were relatively young, six patients (8%) showed apparent renal dysfunction. Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe and the USA.
-
Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe/USA: genetic and clinical studies of 86 unrelated patients with low-molecular-weight proteinuria
Nephrology Dialysis Transplantation, 2013Co-Authors: Takashi Sekine, Fusako Komoda, Mitsunobu Shimadzu, Takeshi Matsuyama, Kenichiro Miura, Akira Ashida, Junko Takita, Takashi IgarashiAbstract:Dent disease is an X-linked disorder characterized by lowmolecular-weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, urolithiasis and renal dysfunction. Dent disease is caused by mutations in at least two genes, i.e. CLCN5 and OCRL1, and its genetic background and phenotypes are common among European countries and the USA. However, only few studies on Dent disease in Japan, which was originally called ‘low-molecular-weight proteinuric disease’, have been reported thus far. In this study, we analysed genetic background and clinical phenotype and laboratory data of 86 unrelated Japanese Dent disease patients. The results demonstrated that the genetic basis of Japanese Dent disease was nearly iDentical to those of Dent disease in other countries. Of 86 unrelated Japanese Dent patients, 61 possessed mutations in CLCN5 (Dent-1), of which 27 were novel mutations; 11 showed mutations in OCRL1 (Dent-2), six of which were novel, and the remaining 14 patients showed no mutations in CLCN5 or OCRL1 (Dent-NI). Despite the similarity in genetic background, hypercalciuria was detected in only 51%, rickets in 2% and nephrocalcinosis in 35%. Although the patients were relatively young, six patients (8%) showed apparent renal dysfunction. Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe and the USA.
Takashi Igarashi - One of the best experts on this subject based on the ideXlab platform.
-
japanese Dent disease has a wider clinical spectrum than Dent disease in europe usa genetic and clinical studies of 86 unrelated patients with low molecular weight proteinuria
Nephrology Dialysis Transplantation, 2014Co-Authors: Fusako Komoda, Mitsunobu Shimadzu, Takeshi Matsuyama, Kenichiro Miura, Akira Ashida, Junko Takita, Takashi Sekine, Takashi IgarashiAbstract:Dent disease is an X-linked disorder characterized by low-molecular-weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, urolithiasis and renal dysfunction. Dent disease is caused by mutations in at least two genes, i.e. CLCN5 and OCRL1, and its genetic background and phenotypes are common among European countries and the USA. However, only few studies on Dent disease in Japan, which was originally called 'low-molecular-weight proteinuric disease', have been reported thus far. In this study, we analysed genetic background and clinical phenotype and laboratory data of 86 unrelated Japanese Dent disease patients. The results demonstrated that the genetic basis of Japanese Dent disease was nearly iDentical to those of Dent disease in other countries. Of 86 unrelated Japanese Dent patients, 61 possessed mutations in CLCN5 (Dent-1), of which 27 were novel mutations; 11 showed mutations in OCRL1 (Dent-2), six of which were novel, and the remaining 14 patients showed no mutations in CLCN5 or OCRL1 (Dent-NI). Despite the similarity in genetic background, hypercalciuria was detected in only 51%, rickets in 2% and nephrocalcinosis in 35%. Although the patients were relatively young, six patients (8%) showed apparent renal dysfunction. Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe and the USA.
-
Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe/USA: genetic and clinical studies of 86 unrelated patients with low-molecular-weight proteinuria
Nephrology Dialysis Transplantation, 2013Co-Authors: Takashi Sekine, Fusako Komoda, Mitsunobu Shimadzu, Takeshi Matsuyama, Kenichiro Miura, Akira Ashida, Junko Takita, Takashi IgarashiAbstract:Dent disease is an X-linked disorder characterized by lowmolecular-weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, urolithiasis and renal dysfunction. Dent disease is caused by mutations in at least two genes, i.e. CLCN5 and OCRL1, and its genetic background and phenotypes are common among European countries and the USA. However, only few studies on Dent disease in Japan, which was originally called ‘low-molecular-weight proteinuric disease’, have been reported thus far. In this study, we analysed genetic background and clinical phenotype and laboratory data of 86 unrelated Japanese Dent disease patients. The results demonstrated that the genetic basis of Japanese Dent disease was nearly iDentical to those of Dent disease in other countries. Of 86 unrelated Japanese Dent patients, 61 possessed mutations in CLCN5 (Dent-1), of which 27 were novel mutations; 11 showed mutations in OCRL1 (Dent-2), six of which were novel, and the remaining 14 patients showed no mutations in CLCN5 or OCRL1 (Dent-NI). Despite the similarity in genetic background, hypercalciuria was detected in only 51%, rickets in 2% and nephrocalcinosis in 35%. Although the patients were relatively young, six patients (8%) showed apparent renal dysfunction. Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe and the USA.
-
ocrl1 mutations in Dent 2 patients suggest a mechanism for phenotypic variability
Nephron Physiology, 2009Co-Authors: Antony E Shrimpton, Takashi Igarashi, Richard R Hoopes, Stephen J Knohl, Paul Hueber, Anita A C Reed, Paul T Christie, Anna Lehman, Colin White, David V MilfordAbstract:Background/Aims: Dent disease is an X-linked renal proximal tubulopathy associated with mutations in CLCN5 (Dent 1) or OCRL1 (Dent 2).
Arend Bokenkamp - One of the best experts on this subject based on the ideXlab platform.
-
Novel OCRL1 mutations in patients with the phenotype of Dent disease.
American journal of kidney diseases : the official journal of the National Kidney Foundation, 2020Co-Authors: Boris Utsch, Marcus R Benz, Stefan Frund, Arend Bokenkamp, Ingo Franke, Nesrin Besbas, Bernd Hoppe, Jörg Dötsch, Stephanie M KarleAbstract:Dent disease is an X-linked tubulopathy frequently caused by mutations affecting the voltage-gated chloride channel and chloride/proton antiporter ClC-5. A recent study showed that defects in OCRL1, encoding a phosphatidylinositol 4,5-bisphosphate 5-phosphatase (Ocrl) and usually found mutated in patients with Lowe syndrome, also can provoke a Dent-like phenotype (Dent 2 disease). We investigated 20 CLCN5-negative males from 17 families with a phenotype resembling Dent disease for defects in OCRL1. In our complete series of 35 families with a phenotype of Dent disease, a mutation in the OCRL1 gene was detected in 6 kindreds. All were novel frameshift (Q70RfsX88 and T121NfsX122, detected twice) or missense mutations (I257T and R476W). None of our patients had cognitive or behavioral impairment or cataracts, 2 classic hallmarks of Lowe syndrome. All patients had mild increases in lactate dehydrogenase and/or creatine kinase levels, which rarely is observed in CLCN5-positive patients, but frequently found in patients with Lowe syndrome. To explain the phenotypic heterogeneity caused by OCRL1 mutations, we performed extensive data-bank mining and extended reverse-transcriptase polymerase chain reaction analysis, which provided no evidence for yet unknown (tissue-specific) alternative OCRL1 transcripts. Mutations in the OCRL1 gene are found in approximately 23% of kindreds with a Dent phenotype. Defective protein sorting/targeting of Ocrl might be the reason for mildly elevated creatine kinase and lactate dehydrogenase serum concentrations in these patients and a clue to suspect Dent disease unrelated to CLCN5 mutations. It remains to be elucidated why the various OCRL1 mutations found in patients with Dent 2 disease do not cause cataracts.
-
proteinuria in Dent disease a review of the literature
Pediatric Nephrology, 2017Co-Authors: Youri Van Berkel, Joanna A E Van Wijk, Michael Ludwig, Arend BokenkampAbstract:Background Dent disease is a rare X-linked recessive proximal tubulopathy caused by mutations in CLCN5 (Dent-1) or OCRL (Dent-2). As a rule, total protein excretion (TPE) is low in tubular proteinuria compared with glomerular disease. Several authors have reported nephrotic-range proteinuria (NP) and glomerulosclerosis in Dent disease. Therefore, we aimed to analyze protein excretion in patients with documented CLCN5 or OCRL mutations in a systematic literature review.
-
Proteinuria in Dent disease: a review of the literature
Pediatric Nephrology, 2017Co-Authors: Youri Van Berkel, Joanna A E Van Wijk, Michael Ludwig, Arend BokenkampAbstract:Background Dent disease is a rare X-linked recessive proximal tubulopathy caused by mutations in CLCN5 (Dent-1) or OCRL (Dent-2). As a rule, total protein excretion (TPE) is low in tubular proteinuria compared with glomerular disease. Several authors have reported nephrotic-range proteinuria (NP) and glomerulosclerosis in Dent disease. Therefore, we aimed to analyze protein excretion in patients with documented CLCN5 or OCRL mutations in a systematic literature review. Design PubMed and Embase were searched for cases with documented CLCN5 or OCRL mutations and (semi-)quantitative data on protein excretion. The most reliable data (i.e., TPE > protein–creatinine ratio > Albustix) was used for NP classification. Results Data were available on 148 patients from 47 reports: 126 had a CLCN5 and 22 an OCRL mutation. TPE was not significantly different between both forms ( p = 0.11). Fifty-five of 126 (43.7 %) Dent-1 vs 13/22 (59.1 %) Dent-2 patients met the definition of NP ( p = 0.25). Serum albumin was normal in all reported cases (24/148). Glomerulosclerosis was noted in 20/32 kidney biopsies and was strongly related to tubulointerstitial fibrosis, but not to kidney function or proteinuria. Conclusion More than half of the patients with both forms of Dent disease have NP, and the presence of low molecular weight proteinuria in a patient with NP in the absence of edema and hypoalbuminemia should prompt genetic testing. Even with normal renal function, glomerulosclerosis and tubulointerstitial fibrosis are present in Dent disease. The role of proteinuria in the course of the disease needs to be examined further in longitudinal studies.
-
Dent 2 disease a mild variant of lowe syndrome
The Journal of Pediatrics, 2009Co-Authors: Arend Bokenkamp, Robert J Unwin, Hae Il Cheong, Velibor Tasic, Detlef Bockenhauer, Bernd Hoppe, Michael LudwigAbstract:Objective To compare the renal and extra-renal phenotypes of patients classified as having Dent disease, Dent-2 disease, or Lowe syndrome. Study design Chart review of data from 93 patients with iDentified voltage-gated chloride channel and chloride/proton antiporter 5 gene and oculo-cerebro-renal syndrome of Lowe gene mutations observed by the authors, complemented with published data. Results There was a wide overlap of renal symptoms. Nephrocalcinosis was more prevalent in Dent-1 disease, and renal tubular acidosis, aminoaciduria, and renal failure was more prevalent in patients with Lowe syndrome. Patients with Lowe syndrome were shorter than patients with Dent-1 disease, and patients with Dent-2 disease showed an intermediate phenotype. Three patients with Dent-2 disease had mild peripheral cataract, and 9 patients were noted to have some degree of mental retardation. Conclusion There is a phenotypic continuum within patients with Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for loss of oculo-cerebro-renal syndrome of Lowe gene function.
-
novel ocrl1 mutations in patients with the phenotype of Dent disease
American Journal of Kidney Diseases, 2006Co-Authors: Boris Utsch, Marcus R Benz, Stefan Frund, Stephanie M Karle, Arend Bokenkamp, Ingo Franke, Nesrin Besbas, Bernd Hoppe, Jörg Dötsch, E KuwertzbrokingAbstract:Background: Dent disease is an X-linked tubulopathy frequently caused by mutations affecting the voltage-gated chloride channel and chloride/proton antiporter ClC-5. A recent study showed that defects in OCRL1 , encoding a phosphatidylinositol 4,5-bisphosphate 5-phosphatase (Ocrl) and usually found mutated in patients with Lowe syndrome, also can provoke a Dent-like phenotype (Dent 2 disease). Methods: We investigated 20 CLCN5 -negative males from 17 families with a phenotype resembling Dent disease for defects in OCRL1 . Results: In our complete series of 35 families with a phenotype of Dent disease, a mutation in the OCRL1 gene was detected in 6 kindreds. All were novel frameshift (Q70R fs X88 and T121N fs X122, detected twice) or missense mutations (I257T and R476W). None of our patients had cognitive or behavioral impairment or cataracts, 2 classic hallmarks of Lowe syndrome. All patients had mild increases in lactate dehydrogenase and/or creatine kinase levels, which rarely is observed in CLCN5 -positive patients, but frequently found in patients with Lowe syndrome. To explain the phenotypic heterogeneity caused by OCRL1 mutations, we performed extensive data-bank mining and extended reverse-transcriptase polymerase chain reaction analysis, which provided no evidence for yet unknown (tissue-specific) alternative OCRL1 transcripts. Conclusion: Mutations in the OCRL1 gene are found in approximately 23% of kindreds with a Dent phenotype. Defective protein sorting/targeting of Ocrl might be the reason for mildly elevated creatine kinase and lactate dehydrogenase serum concentrations in these patients and a clue to suspect Dent disease unrelated to CLCN5 mutations. It remains to be elucidated why the various OCRL1 mutations found in patients with Dent 2 disease do not cause cataracts.
Michael Ludwig - One of the best experts on this subject based on the ideXlab platform.
-
proteinuria in Dent disease a review of the literature
Pediatric Nephrology, 2017Co-Authors: Youri Van Berkel, Joanna A E Van Wijk, Michael Ludwig, Arend BokenkampAbstract:Background Dent disease is a rare X-linked recessive proximal tubulopathy caused by mutations in CLCN5 (Dent-1) or OCRL (Dent-2). As a rule, total protein excretion (TPE) is low in tubular proteinuria compared with glomerular disease. Several authors have reported nephrotic-range proteinuria (NP) and glomerulosclerosis in Dent disease. Therefore, we aimed to analyze protein excretion in patients with documented CLCN5 or OCRL mutations in a systematic literature review.
-
Proteinuria in Dent disease: a review of the literature
Pediatric Nephrology, 2017Co-Authors: Youri Van Berkel, Joanna A E Van Wijk, Michael Ludwig, Arend BokenkampAbstract:Background Dent disease is a rare X-linked recessive proximal tubulopathy caused by mutations in CLCN5 (Dent-1) or OCRL (Dent-2). As a rule, total protein excretion (TPE) is low in tubular proteinuria compared with glomerular disease. Several authors have reported nephrotic-range proteinuria (NP) and glomerulosclerosis in Dent disease. Therefore, we aimed to analyze protein excretion in patients with documented CLCN5 or OCRL mutations in a systematic literature review. Design PubMed and Embase were searched for cases with documented CLCN5 or OCRL mutations and (semi-)quantitative data on protein excretion. The most reliable data (i.e., TPE > protein–creatinine ratio > Albustix) was used for NP classification. Results Data were available on 148 patients from 47 reports: 126 had a CLCN5 and 22 an OCRL mutation. TPE was not significantly different between both forms ( p = 0.11). Fifty-five of 126 (43.7 %) Dent-1 vs 13/22 (59.1 %) Dent-2 patients met the definition of NP ( p = 0.25). Serum albumin was normal in all reported cases (24/148). Glomerulosclerosis was noted in 20/32 kidney biopsies and was strongly related to tubulointerstitial fibrosis, but not to kidney function or proteinuria. Conclusion More than half of the patients with both forms of Dent disease have NP, and the presence of low molecular weight proteinuria in a patient with NP in the absence of edema and hypoalbuminemia should prompt genetic testing. Even with normal renal function, glomerulosclerosis and tubulointerstitial fibrosis are present in Dent disease. The role of proteinuria in the course of the disease needs to be examined further in longitudinal studies.
-
Dent 2 disease a mild variant of lowe syndrome
The Journal of Pediatrics, 2009Co-Authors: Arend Bokenkamp, Robert J Unwin, Hae Il Cheong, Velibor Tasic, Detlef Bockenhauer, Bernd Hoppe, Michael LudwigAbstract:Objective To compare the renal and extra-renal phenotypes of patients classified as having Dent disease, Dent-2 disease, or Lowe syndrome. Study design Chart review of data from 93 patients with iDentified voltage-gated chloride channel and chloride/proton antiporter 5 gene and oculo-cerebro-renal syndrome of Lowe gene mutations observed by the authors, complemented with published data. Results There was a wide overlap of renal symptoms. Nephrocalcinosis was more prevalent in Dent-1 disease, and renal tubular acidosis, aminoaciduria, and renal failure was more prevalent in patients with Lowe syndrome. Patients with Lowe syndrome were shorter than patients with Dent-1 disease, and patients with Dent-2 disease showed an intermediate phenotype. Three patients with Dent-2 disease had mild peripheral cataract, and 9 patients were noted to have some degree of mental retardation. Conclusion There is a phenotypic continuum within patients with Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for loss of oculo-cerebro-renal syndrome of Lowe gene function.
