title: A novel mutation of COL4A3 presents a different contribution to Alport syndrome and thin basement membrane nephropathy.
abstract: BACKGROUND
  Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are heterogeneous renal hereditary diseases. Mutations of COL4A3 and COL4A4 genes were reported to be the underlying pathogenicity in both diseases. However, the mechanism of the same mutation causing totally different clinical processes and outcomes in AS and TBMN is still not clear.
  
  
  METHODS
  Mutations of all coding exons of COL4A3 and COL4A4 were screened in a patient with autosomal recessive Alport syndrome (ARAS) of a Chinese Han consanguineous family by means of PCR and direct sequencing. Furthermore, the identified mutation was validated by restriction endonuclease AvaII in all 20 members in his family, as well as 46 patients with TBMN, 2 patients with AS from another two families, and 50 healthy controls.
  
  
  RESULTS
  A novel missense mutation (3725G>A, G1242D) in exon 42 of COL4A3 was identified in the proband in the homozygous form. This pathogenic mutation was demonstrated in all carriers who presented with hematuria or mild proteinuria in the heterozygous form, whereas it was not detected in others whose urinalysis was normal within the family. In addition, 10 polymorphisms, including 1 non-glycine missense variant and 9 neutral polymorphisms, were detected in COL4A3/COL4A4.
  
  
  CONCLUSIONS
  The novel mutation (3725G>A, G1242D) of COL4A3 was the underlying pathogenic role in the homozygous form in ARAS and in the heterozygous form in TBMN within an identical family. The result provided a potentially useful clue for the functional investigation of COL4A3 in these two hereditary glomerular disorders.
authors.affiliation: Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hou
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Ding
authors.forename: Guangtao
authors.initials: G
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000225:Adenine; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001224:Aspartic Acid; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D024141:Collagen Type IV / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D050533:Glomerular Basement Membrane / Q000473:pathology*; D005998:Glycine; D006147:Guanine; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D020125:Mutation, Missense; D009394:Nephritis, Hereditary / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D001324:Autoantigens; C466620:COL4A4 protein, human; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain; D001224:Aspartic Acid; D006147:Guanine; D000225:Adenine; D005998:Glycine