Disease relevance of Nephritis, Hereditary

• Our results demonstrate that Lmx1b regulates important steps in glomerular development and establish a link between three hereditary kidney diseases: nail-patella syndrome (Lmx1b), steroid-resistant nephrotic syndrome (podocin), and Alport syndrome (collagen IV alpha4) [1].
• Deletion of alpha(1) integrin results in decreased accumulation of both myofibroblasts and macrophages in the tubular interstitium in Alport's syndrome mice and delays disease progression [2].
• Gelatinase B-deficient mice were bred with Col4a3-/- mice, a model for Alport syndrome, to determine whether gelB influences the progression of glomerulonephritis [3].
• The present study examined the effect of cyclosporine A on GBM structure and the progression to renal failure in a canine model of X-linked Alport syndrome [4].
• We report an additional case with Alport's syndrome associated with leiomyomatosis carrying a deletion of both COL4A5 and COL4A6 genes [5].

Psychiatry related information on Nephritis, Hereditary

• Our recent discovery of the contiguous gene deletion syndrome ATS-MR (previously known as Alport syndrome, mental retardation, midface hypoplasia, elliptocytosis, OMIM #300194), characterized by Alport syndrome (ATS) and mental retardation (MR), indicated Xq22.3 as a region containing one mental retardation gene [6].

High impact information on Nephritis, Hereditary

• Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome [7].
• In humans, mutation of the collagen alpha 3, alpha 4, or alpha 5(IV) chain genes results in a delayed onset renal disease called Alport syndrome [8].
• Moreover, it is demonstrated that MYH9 mutations also result in two other FTNS-like macrothrombocytopenia syndromes: Epstein syndrome (EPS) and Alport syndrome with macrothrombocytopenia (APSM) [9].
• Determination of the genomic structure of the COL4A4 gene and of novel mutations causing autosomal recessive Alport syndrome [10].
• Substitution of arginine for glycine 325 in the collagen alpha 5 (IV) chain associated with X-linked Alport syndrome: characterization of the mutation by direct sequencing of PCR-amplified lymphoblast cDNA fragments [11].

Chemical compound and disease context of Nephritis, Hereditary

• De novo mutation in the COL4A5 gene converting glycine 325 to glutamic acid in Alport syndrome [12].
• Complete amino acid sequence of the human alpha 5 (IV) collagen chain and identification of a single-base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in an Alport syndrome patient [13].
• Pro-HNP, a urine protein isolated from hereditary nephritis patients, is derived from C3 and resembles the C3c domain [14].
• The surface density of the peripheral GBM correlated with creatinine clearance in Alport syndrome patients (r = 0.71, P < 0.01) [15].
• These findings indicate that cyclosporine A is beneficial in slowing, but not stopping, the clinical and pathologic progression of Alport syndrome [4].

Biological context of Nephritis, Hereditary

• The type IV collagen alpha 5 chain (COL4A5) gene of 88 unrelated male patients with X-linked Alport syndrome was tested for major gene rearrangements by Southern blot analysis, using COL4A5 cDNA probes [16].
• We report here the complete characterization of the 48 exons of the COL4A4 gene, a comprehensive gene screen, and the subsequent detection of 10 novel mutations in eight patients diagnosed with autosomal recessive Alport syndrome [10].
• Missense mutations in the COL4A5 gene in patients with X-linked Alport syndrome [17].
• Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2 [18].
• The majority of cases (about 85%) are caused by mutations in the COL4A5 gene on the X chromosome which encodes the type IV collagen alpha5 chain (X-linked Alport syndrome) [19].

Anatomical context of Nephritis, Hereditary

• In earlier studies, intragenic deletions of COL4A5 were detected in a subset of patients with Alport syndrome (AS), a hereditary defect of basement membranes [20].
• Mutations in either the COL4A3 or the COL4A4 genes, encoding the alpha3 and alpha4 chains of type IV collagen, are responsible for the autosomal-recessive form of Alport syndrome, a progressive hematuric nephropathy characterized by glomerular basement membrane abnormalities [21].
• Mutations in the COL4A5 gene in Alport syndrome: a possible mutation in primordial germ cells [22].
• Splicing mutations in the COL4A5 gene in Alport's syndrome: different mRNA expression between leukocytes and fibroblasts [23].
• ABR were used to document the altered acoustic-nerve conduction and transmission typical of the early stage of Alport's syndrome [24].

Gene context of Nephritis, Hereditary

• A large kindred with adult-type X-linked Alport syndrome was studied with regard to a defect in the recently described COL4A5 collagen gene [11].
• The autosomal recessive form of Alport syndrome is caused by mutations in the COL4A3 and COL4A4 genes, located at 2q35-37 [25].
• The predominant form of Alport syndrome is X-linked; more than 160 different mutations have yet been identified in the type IV collagen alpha 5 chain (COL4A5) gene, located at Xq22-24 head to head to the COL4A6 gene [25].
• COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome [26].
• X-linked Alport syndrome is a progressive renal disease caused by mutations in the COL4A5 gene, which encodes the alpha 5(IV) collagen chain [27].

Analytical, diagnostic and therapeutic context of Nephritis, Hereditary

• Gene therapy has the potential to provide a therapeutic strategy for numerous renal diseases such as diabetic nephropathy, chronic rejection, Alport syndrome, polycystic kidney disease, and inherited tubular disorders [28].
• It is concluded that PCR amplification and direct DNA sequencing of the promoter and exons is currently the best procedure to detect mutations in COL4A5 in Alport syndrome [18].
• The aim of this study was to assess urinary IGF-I, IGF-II, and IGFBP-3 in a cross-sectional study of healthy subjects, as well as characterize urinary IGFBPs (uIGFBps) in patients with GH deficiency (GHD) and renal disease, such as, Alport syndrome, immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and systemic lupus erythematosus [29].
• Identification of COL4A5 defects in Alport's syndrome by immunohistochemistry of skin [30].
• Detection of mutations in the COL4A5 gene in over 90% of male patients with X-linked Alport's syndrome by RT-PCR and direct sequencing [31].

References