Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pedigree of a line of Samoyed dogs with Samoyed hereditary glomerulopathy (SHG) was investigated to determine the mode of inheritance. Sixty percent of males were affected with severe renal disease that progressed to renal failure before 15 months of age. In contrast, female carriers showed less severe involvement and their disease did not progress to renal failure. This pattern is consistent with the inheritance of an X-linked dominant gene. A similar mode of inheritance has been postulated in some families with hereditary nephritis. Further similarities between SHG in dogs and hereditary nephritis in humans have been demonstrated previously in clinical and renal morphologic studies. The present study supports the view that this line of Samoyed dogs would be an appropriate model for studying the human disease.
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PMID:Mode of inheritance of Samoyed hereditary glomerulopathy: an animal model for hereditary nephritis in humans. 371 21

Nephrogenic diabetes insipidus usually presents with polyuria, polydipsia, fever, vomiting, dehydration and failure to thrive. However, in infancy polyuria may be absent because of dehydration and reduced glomerular filtration rate. In 2 cases the main presenting feature was hypotonia, with marked head lag. Family studies confirmed the X-linked mode of inheritance of the disease; in case 1 the disease appeared to have arisen as a new mutation in the mother, and in case 2 the carrier status was traced back to the great-grandmother. Pitfalls in the diagnosis and detection of the carriers are discussed. Treatment with thiazide diuretics and prostaglandin synthesis inhibitors is effective in reducing urine volumes and polydipsia. The early detection of the disease and adequate management may prevent such complications as megacystis, mega-ureter and hydronephrosis, with resulting renal failure. Mental and physical retardation may also be avoided.
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PMID:Nephrogenic diabetes insipidus presenting with infantile hypotonia. A report of 2 cases. 373 62

Forty-one families have been studied with stringent diagnostic criteria of Alport syndrome: proven renal disease with hematuria affecting at least two relatives, neural hearing loss in at least one affected individual, and evolution to renal failure in at least one affected individual. The proportion of affected offsprings of affected females does not significantly differ from the ratio expected for a dominant trait. The descendance of affected males shows a lack of affected males. In four families, with parental consanguinity and nonaffected parents, the findings agree with an autosomal recessive inheritance. Study of quantitative traits such as death or renal death among brothers, uncle-nephew pairs and whole families shows evident intra-familial resemblances. We conclude that Alport syndrome seems to be a heterogeneous state composed of a number of genetically distinct syndromes, with an autosomal dominant, an X-linked dominant, and an autosomal recessive form.
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PMID:Genetic heterogeneity of Alport syndrome. 401 Jan 53

A five-year-old girl presented with mental retardation (MR), microcephaly, short stature, ptosis, malocclusion, abnormal elbows, fifth finger clinodactyly, joint hyperextensibility in hands and feet, renal hypoplasia, nonobstructive ureteral stasis, pyelonephritis, and renal failure. Five X chromosomes (49,XXXXX) were found in all peripheral blood lymphocytes and skin fibroblasts examined. Xa RBC typing, utilizing serial dilutions of antiserum, gave agglutination at a higher titer than in either Xg(a+) positive parent; the patient's serum IgM was also elevated. These immunological findings imply a lack of dosage compensation and incomplete inactivation of some X-linked loci.
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PMID:Pentasomy X: report of patient and studies of X-inactivation. 724 3

Type IV collagen is a complex molecule composed of three alpha chains that can be of types alpha 1(IV) to alpha 5(IV). Each alpha chain contains an amino-terminal collagenous domain and a carboxyl-terminal noncollagenous (NC) domain consisting of 229 amino acids, which is involved in intermolecular cross-linking to construct the basement membrane network. Specific localization of alpha 5(IV) collagen in glomerular basement membranes (GBM) in the kidney indicates its crucial role for that construction. In human kidney cortex and skin RNA, we found an alternative splicing transcript which skips exon 50 of the alpha 5(IV) collagen gene using reverse transcription-polymerase chain reaction and direct sequencing of the PCR products. This alternative splicing introduces a stop codon at the first codon of exon 51, resulting in an mRNA encoding a protein lacking the 84 NC domain carboxylterminal amino acid residues encoded by exons 50 and 51. Recently, gene mutations affecting the alpha 5(IV) collagen NC domain have been reported in patients with X-linked Alport syndrome who display GBM destruction and progressive renal failure, which are usually milder in female patients. Therefore, the alternative splicing, if its truncated products are dominantly expressed in glomeruli, may cause GBM impairment and renal failure progression.
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PMID:Alternative splicing in the alpha 5(IV) collagen gene in human kidney and skin tissues. 750 7

The X-linked form of Alport disease, caused by mutations in the COL4A5 or the COL4A6 gene, usually leads to terminal renal failure in males, while affected females have a more variable and moderate phenotype. We detected in a female patient, with a severe Alport phenotype, two new missense mutations. One mutation (G289V) occurred in exon 15 and converted a glycine in a collagenous domain of COL4A5 to a valine. The second mutation, located in exon 46, substituted a cysteine proximal to the NC1 domain of COL4A5 for an arginine. In white blood cells and kidney both mutations were present on > 90% of the mRNA, while at the genomic level the patient was heterozygous for both mutations. The two mutations therefore occurred in the same COL4A5 allele. No mutation was found in the COL4A5 promoter region by sequencing nor was a major rearrangement of the normal allele detected. A skewed pattern of X inactivation was demonstrated in DNA isolated from the patient's kidney and white blood cells: > 90% of the X chromosomes with the normal COL4A5 allele was inactivated. It is suggested that this skewed inactivation pattern is responsible for the absence of detectable normal COL4A5 mRNA and hence the severe phenotype in this woman.
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PMID:Severe alport phenotype in a woman with two missense mutations in the same COL4A5 gene and preponderant inactivation of the X chromosome carrying the normal allele. 770 90

We describe here a patient with familial interstitial nephritis and albipunctatus retinopathy. Albipunctatus is often seen in patients with Alport syndrome, which is an X-linked disorder characterised in affected males by renal failure by the age of 25, high-tone sensorineural deafness, anterior lenticonus and albipunctatus. The diagnosis of Alport syndrome depends on the electron microscopic appearance of a trabeculated glomerular basement membrane (GBM); and mutations have been demonstrated in the gene for the alpha 5 chain of type IV collagen. In the familial interstitial nephritis described here, the inheritance was autosomal dominant, renal failure developed in middle age, and there was no associated hearing loss or anterior lenticonus. The finding of albipunctatus retinopathy in this patient suggests that the genetic mutation responsible involves a protein common to both retinal and interstitial basement membranes. In addition, we conclude that the demonstration of albipunctatus in an individual with familial nephritis does not necessarily indicate that the underlying disease is Alport syndrome.
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PMID:Albipunctatus retinopathy in inherited interstitial nephritis. 772 5

Bull terrier hereditary nephritis is inherited as an autosomal dominant disease and causes renal failure at variable ages in affected dogs. The aims of this study were to compare the clinical, ultrastructural and immunohistochemical features of bull terrier hereditary nephritis with the characteristics of the human forms of Alport syndrome. Many animals with bull terrier hereditary nephritis have hematuria, and some have anterior lenticonus. However, deafness is not associated with the renal disease, and affected dogs do not have the large platelets that are occasionally seen in patients with autosomal Alport syndrome. The glomerular capillary basement membrane (GCBM) in affected bull terriers has an identical ultrastructural appearance to that seen in X-linked Alport syndrome, with lamellations and intramembranous electron-dense deposits. However, both the Goodpasture and the Alport antigens, which represent parts of the alpha 3(IV) and alpha 5(IV) collagen chains, respectively, are present in the GCBM of affected dogs. Bull terrier hereditary nephritis represents an animal model for autosomal dominant Alport syndrome, and can be used to further examine how genetic mutations affect a basement membrane protein and the corresponding membrane structure.
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PMID:Bull terrier hereditary nephritis: a model for autosomal dominant Alport syndrome. 775 74

Dent's disease, an X-linked renal tubular disorder, is a form of Fanconi syndrome which is characterized by proteinuria, hypercalciuria, nephrocalcinosis, kidney stones and renal failure. Previous studies localised the gene responsible to Xp11.22, within a microdeletion involving the hypervariable locus DXS255. Further analysis using new probes which flank this locus indicate that the deletion is less than 515 kb. A 185 kb YAC containing DXS255 was used to screen a cDNA library from adult kidney in order to isolate coding sequences falling within the deleted region which may be implicated in the disease aetiology. We identified two clones which are evolutionarily conserved, and detect a 9.5 kb transcript which is expressed predominantly in the kidney. Sequence analysis of 780 bp of ORF from the clones suggests that the identified gene, termed hCIC-K2, encodes a new member of the CIC family of voltage-gated chloride channels. Genomic fragments detected by the cDNA clones are completely absent in patients who have an associated microdeletion. On the basis of the expression pattern, proposed function and deletion mapping, hCIC-K2 is a strong candidate for Dent's disease.
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PMID:Isolation and partial characterization of a chloride channel gene which is expressed in kidney and is a candidate for Dent's disease (an X-linked hereditary nephrolithiasis). 787 26

Alport syndrome (AS) is an hereditary disease of basement membranes characterized by progressive renal failure and deafness. Changes in the glomerular basement membrane (GBM) in AS suggest that the type IV collagen matrix, the major structural component of GBM, is disrupted. We recently isolated the genes for two type IV collagens, alpha 3(IV) and alpha 4(IV), that are encoded head-to-head on human chromosome 2. These chains are abundant in normal GBM but are sometimes absent in AS. We screened for mutations in families in which consanguinity suggested autosomal recessive inheritance. Homozygous mutations were found in alpha 3(IV) in two families and in alpha 4(IV) in two others, demonstrating that these chains are important in the structural integrity of the GBM and that there is an autosomal form of AS in addition to the previously-defined X-linked form.
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PMID:Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. 798 96


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