Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9477
Title: Mutations in the COL4A4 gene in thin basement membrane disease.
Authors: Buzza, Mark;Dagher, Hayat;Wang, Yan Yan;Wilson, Diane;Babon, Jeffrey J;Cotton, Richard G;Savige, Judy A
Affiliation: University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Australia.
Issue Date: 1-Feb-2003
Citation: Kidney International; 63(2): 447-53
Abstract: Patients with thin basement membrane disease (TBMD) are often from families where hematuria segregates with the COL4A3 and COL4A4 genes. These genes also are affected in autosomal recessive Alport syndrome. The aim of this study was to demonstrate COL4A4 mutations in TBMD.Forty-eight unrelated individuals with TBMD who had no family members with autosomal recessive Alport syndrome were examined for COL4A4 mutations. The diagnosis of TBMD had been confirmed by renal biopsy (43/48, 90%) or by a family history of hematuria but without a renal biopsy (5/48, 10%). The 47 coding exons of COL4A4 were screened for mutations with the methods of enzyme mismatch cleavage or single stranded conformational polymorphism (SSCP) analysis, and exons that demonstrated electrophoretic abnormalities were sequenced.Nine variants that altered the coding sequences were identified. These were nonsense and frameshift mutations that resulted in stop codons (N = 3), and glycine (N = 3) and non-glycine missense variants (N = 3). Four intronic variants and three neutral polymorphisms were also detected. In total, four variants were considered 'pathogenic' principally because they resulted in stop codons or were not present in non-hematuric normal subjects. Three variants were considered 'possibly pathogenic' but two of these were each present in one of 46 non-hematuric normal subjects.Pathogenic COL4A4 mutations were demonstrated in three of the nine (33%) families in whom hematuria segregated with the COL4A3/COL4A4 locus. Two stop codons (R1377X and 2788/91delG) and a glycine substitution (G960R) resulted in hematuria in all 16 members who were tested from these three families. The S969X mutation described here in TBMD for the first time, as well as the R1377X mutation, also occur in autosomal recessive Alport syndrome.
Internal ID Number: 12631110
URI: http://ahro.austin.org.au/austinjspui/handle/1/9477
DOI: 10.1046/j.1523-1755.2003.00780.x
URL: http://www.ncbi.nlm.nih.gov/pubmed/12631110
Type: Journal Article
Subjects: Adolescent
Adult
Aged
Amino Acid Substitution
Basement Membrane.pathology
Child
Codon, Nonsense
Codon, Terminator
Collagen Type IV.genetics
Female
Frameshift Mutation
Glycine
Hematuria.genetics.pathology
Humans
Male
Middle Aged
Mutation
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.