Hereditary nephritis (with unusual renal histology): report of a first case from the West Indies.
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A 21-year-old Grenadian girl undergoing investigation in Trinidad for anaemia was diagnosed as a case of hereditary nephritis. She had the clinical features of a nephropathy, nerve deafness and an ocular defect. Renal histology was exceptional in that in addition to the typical findings of a hereditary nephritis, cystic areas generally associated with medullary cystic disease were noted. Several members of the patient's maternal family were afflicted with either deafness visual distrubances or renal disease. (+info)
Nephronophthisis in Finland: epidemiology and comparison of genetically classified subgroups.
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Nephronophthisis--medullary cystic kidney disease is a progressive chronic tubulointerstitial nephritis leading to terminal renal failure. About two thirds of the patients with familial juvenile nephronophthisis, an autosomal recessive disease, have a homozygous deletion at the gene locus on 2q13. Through a nationwide search, 59 patients were ascertained in Finland. The incidence was 1:61,800 live births when calculated over a 20-year period. Of the patients, 17 came from four families showing dominant inheritance and 37 patients from 28 apparently recessive families when classified by family history, clinical features or presence of a deletion on 2q13. Two were considered as new dominant mutations; three sporadic patients could not be classified. The most significant difference between the patients with deletions, patients without deletions but having recessive family history, and patients belonging to families with dominant inheritance was the age at first symptoms, at the start of dialysis and at transplantation. These facts will be of help in determining the mode of inheritance of a sporadic patient without a deletion. (+info)
Renal function after tumor enucleation: assessment by quantitative SPECT of 99mTc-dimercaptosuccinic acid uptake by the kidneys.
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The purpose of this study was to evaluate the amount of functioning renal mass removed and the amount of remaining individual renal function after tumor enucleation. METHODS: Renal functional volume, percentage injected dose (%ID) per cubic centimeter of renal tissue and individual renal uptake of 24 operated and 24 contralateral kidneys were studied by two sequential SPECT quantitations of 99mTc-dimercaptosuccinic acid (DMSA) uptake by the kidneys (QDMSA). The first study was before surgery and the second study was 1 to 6 mo (mean 3.5 mo) after surgery. Mean tumor size was 3.4 +/- 0.99 cm and all tumors were confined to the renal parenchyma (stages pT1 and pT2). RESULTS: In the operated kidneys, there was a statistically significant decrease in renal cortical volume (170 +/- 46 mL after surgery versus 207 +/- 45 mL before surgery, t = 6.2, P < 0.001) and individual renal uptake (10.3% +/- 3.0% after surgery versus 13.0% +/- 2.9% before surgery, t = 5.4, P < 0.001). There was no statistically significant change after surgery compared with before surgery in the %ID per cubic centimeter of renal tissue of the operated kidneys, and in the volume, %ID per cubic centimeter and uptake of the contralateral normal kidneys. CONCLUSION: The results suggest that QDMSA is a noninvasive method able to assess changes in separate renal function. The limited functioning parenchymal loss after tumor enucleation had no effect on the opposite kidneys. (+info)
Contrast-enhanced power Doppler sonography for the differentiation of cystic renal lesions: preliminary study.
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The objective of this study was to investigate the potential usefulness of contrast-enhanced power Doppler ultrasonography in the differentiation of benign and malignant cystic renal lesions. Our study group was limited to patients who had complex cystic renal lesions of uncertain malignancy at screening ultrasonography. During the previous 6 months, 485 patients have been referred to ultrasonography for evaluation of renal cystic lesions, but only 13 patients participated in this study. Focusing on tumor vascularity in the intracystic septa or solid component, we analyzed power Doppler sonographic images before and after intravenous injection of contrast agent and compared them with contrast-enhanced CT scans or MR images and pathologic results. The visualization of vascularity was best on contrast-enhanced power Doppler sonography (n = 7). The use of contrast agent with power Doppler sonography showed improved diagnostic accuracy (77%) that was superior to non-contrast-enhanced power Doppler sonography or contrast-enhanced CT. In conclusion, contrast-enhanced power Doppler sonography provides better visualization of tumor vascularity in complicated cystic renal lesions than other imaging modalities, leading to more exact differential diagnosis. We therefore expect that this imaging modality might be very useful in differential diagnosis of problematic cystic renal lesions, benign or malignant. (+info)
A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta.
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Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor (HNF)-1beta are the cause of one form of maturity-onset diabetes of the young (MODY), type 5 (MODY5). We have studied a Norwegian family, N5, with a syndrome of mild diabetes, progressive non-diabetic renal disease and severe genital malformations. The sequence of the HNF-1beta gene ( TCF2 ) revealed a 75 bp deletion in exon 2 (409-483del) which would result in the synthesis of a protein lacking amino acids Arg137 to Lys161 (R137-K161del). This deletion is located in the pseudo-POU region of HNF-1beta, a region implicated in the specificity of DNA binding. Functional studies of R137-K161del HNF-1beta revealed that it could not bind an HNF-1 target sequence or stimulate transcription of a reporter gene indicating that this is a loss-of-function mutation. The R137-K161del allele co-segregated with diabetes and renal disease in pedigree N5. In addition, two of four female carriers with this mutation had vaginal aplasia and rudimentary uterus (Mullerian aplasia). These studies strongly suggest that heterozygous mutations in the HNF-1beta gene are associated with a syndrome characterized by MODY and severe, non-diabetic renal disease. Moreover, the presence of internal genital malformations in two females suggests that additional clinical features may be associated with HNF-1beta mutations. (+info)
Identification of a new gene locus for adolescent nephronophthisis, on chromosome 3q22 in a large Venezuelan pedigree.
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Nephronophthisis, an autosomal-recessive cystic kidney disease, is the most frequent monogenic cause for renal failure in childhood. Infantile and juvenile forms of nephronophthisis are known to originate from separate gene loci. We describe here a new disease form, adolescent nephronophthisis, that is clearly distinct by clinical and genetic findings. In a large, 340-member consanguineous Venezuelan kindred, clinical symptoms and renal pathology were evaluated. Onset of terminal renal failure was compared with that in a historical sample of juvenile nephronophthisis. Onset of terminal renal failure in adolescent nephronophthisis occurred significantly later (median age 19 years, quartile borders 16.0 and 25.0 years) than in juvenile nephronophthisis (median age 13.1 years, quartile borders 11.3 and 17.3 years; Wilcoxon test P=.0069). A total-genome scan of linkage analysis was conducted and evaluated by LOD score and total-genome haplotype analyses. A gene locus for adolescent nephronophthisis was localized to a region of homozygosity by descent, on chromosome 3q22, within a critical genetic interval of 2. 4 cM between flanking markers D3S1292 and D3S1238. The maximum LOD score for D3S1273 was 5.90 (maximum recombination fraction.035). This locus is different than that identified for juvenile nephronophthisis. These findings will have implications for diagnosis and genetic counseling in hereditary chronic renal failure and provide the basis for identification of the responsible gene. (+info)
Molecular genetics of nephronophthisis and medullary cystic kidney disease.
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Nephronophthisis (NPH) and medullary cystic kidney disease (MCKD) constitute a group of renal cystic diseases that share the macroscopic feature of cyst development at the corticomedullary border of the kidneys. The disease variants also have in common a characteristic renal histologic triad of tubular basement membrane disintegration, tubular atrophy with cyst development, and interstitial cell infiltration with fibrosis. NPH and, in most instances, MCKD lead to chronic renal failure with an onset in the first two decades of life for recessive NPH and onset in adult life for autosomal dominant MCKD. There is extensive genetic heterogeneity with at least three different loci for NPH (NPHP1, NPHP2, and NPHP3) and two different loci for MCKD (MCKD1 and MCKD2). Juvenile nephronophthisis, in addition, can be associated with extrarenal organ involvement. As a first step toward understanding the pathogenesis of this disease group, the gene (NPH1) for juvenile nephronophthisis (NPH1) has been identified by positional cloning. Its gene product, nephrocystin, is a novel protein of unknown function that contains a src-homology 3 domain. It is hypothesized that the pathogenesis of NPH might be related to signaling processes at focal adhesions (the contact points between cells and extracellular matrix) and/or adherens junctions (the contact points between cells). This hypothesis is based on the fact that most src-homology 3-containing proteins are part of focal adhesion signaling complexes, on animal models that exhibit an NPH-like phenotype, and on the recent finding that nephrocystin binds to the protein p130(cas), a major mediator of focal adhesion signaling. (+info)
Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease.
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Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown. Mutations in the gene encoding hepatocyte nuclear factor (HNF)-1beta have been associated with early-onset diabetes and nondiabetic renal disease-particularly renal cystic disease. We investigated a possible role for the HNF-1beta gene in four unrelated GCKD families and identified mutations in two families: a nonsense mutation in exon 1 (E101X) and a frameshift mutation in exon 2 (P159fsdelT). The family members with HNF-1beta gene mutations had hypoplastic GCKD and early-onset diabetes or impaired glucose tolerance. We conclude that there is genetic heterogeneity in familial GCKD and that the hypoplastic subtype is a part of the clinical spectrum of the renal cysts and diabetes syndrome that is associated with HNF-1beta mutations. (+info)