title: The genetics of thin basement membrane nephropathy.
abstract: The diagnosis of thin basement membrane nephropathy (TBMN) usually is made on the basis of the clinical features or the glomerular membrane ultrastructural appearance. Only now are we beginning to understand the genetics of TBMN and the role of diagnostic genetic testing. The similarity of clinical and glomerular membrane features first suggested TBMN might represent the carrier state for autosomal-recessive Alport syndrome. This was confirmed subsequently by the demonstration that 40% of families with TBMN have hematuria that segregates with the corresponding locus ( COL4A3/COL4A4 ), and identical mutations occur in both conditions. To date, about 20 COL4A3 and COL4A4 mutations have been shown in TBMN, and these mainly are single nucleotide substitutions that are different in each family. The families in whom hematuria does not appear to segregate with the COL4A3/COL4A4 locus cannot all be explained by de novo mutations, and nonpenetrant or coincidental hematuria. This suggests a further TBMN locus. In patients with persistent hematuria, testing for COL4A3 and COL4A4 mutations to diagnose TBMN is problematic because of the huge size of these genes, their frequent polymorphisms, and the likelihood of a further gene locus. It is far more practicable to perform genetic testing to exclude or confirm X-linked Alport syndrome because this condition is the major differential diagnosis of TBMN and has a very different prognosis.
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health/Northern Health, The Northern Hospital, Epping, Victoria, Australia.
authors.forename: Kesha
authors.initials: K
authors.lastname: Rana
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Wang
authors.forename: Mark
authors.initials: M
authors.lastname: Buzza
authors.forename: Stephen
authors.initials: S
authors.lastname: Tonna
authors.forename: Ke Wei
authors.initials: KW
authors.lastname: Zhang
authors.forename: Tina
authors.initials: T
authors.lastname: Lin
authors.forename: Lydia
authors.initials: L
authors.lastname: Sin
authors.forename: Smitha
authors.initials: S
authors.lastname: Padavarat
authors.forename: Judy
authors.initials: J
authors.lastname: Savige
mesh_terms: D001324:Autoantigens / Q000235:genetics*; D024141:Collagen Type IV / Q000235:genetics*; D003937:Diagnosis, Differential; D005787:Gene Frequency; D005821:Genetic Techniques; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: D001324:Autoantigens; C466620:COL4A4 protein, human; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain