title: Immunohistochemical study for the diagnosis of Alport's syndrome.
abstract: BACKGROUND
  Alport's syndrome (AS) is the most common cause of inherited glomerular disease in Thailand. The majority of cases show X-linked inheritance, which is caused by mutations in the gene coding for the alpha5 chain of type IV collagen in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM). Such mutation usually leads to a reduction in protein amount, thus, immunohistochemical studies have been considered in diagnostic evaluation.
  
  
  OBJECTIVE
  To study the expression of alpha[IV] collagen chains in the skin as an alternative approach to diagnose AS.
  
  
  METHODS
  Eleven unrelated probands with proven AS, 7 relatives with abnormal urinalysis, 4 suspected individuals, and 8 normal controls were enrolled. A punch skin biopsy and immunofluorescence staining of the tissue specimens for alpha1, alpha3 and alpha5[IV] collagen chains was performed.
  
  
  RESULTS
  The alpha5[IV] chain was absent in the EBM in all male AS patients while a discontinuing pattern was observed in all females except one. The findings are specific for AS with a sensitivity of 91%. Studies in relatives and suspected individuals also confirmed the advantage of this approach as demonstrated by the absence and discontinuation of alpha5[IV] staining in all males and females, respectively. We also analyzed their expressions in the kidney tissue and demonstrated abnormal alpha3 and alpha5[IV] staining in five of six samples.
  
  
  CONCLUSIONS
  Immunohistochemical study of the skin should be used as a screening method in patients suspected of AS, as it is much less invasive. Moreover, it is a useful adjunct to conventional examination of biopsied renal tissue.
authors: Renal Division, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Pimpong
authors: P
authors: Wongtrakul
authors: Chairat
authors: C
authors: Shayakul
authors: Paisal
authors: P
authors: Parichatikanond
authors: Puan
authors: P
authors: Suthipinittharm
authors: Chalongrat
authors: C
authors: Amjaroen
authors: Naparat
authors: N
authors: Kaewkaukul
authors: Arun
authors: A
authors: Vongirad
authors: Leena
authors: L
authors: Ongajyooth
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008297:Male; D008403:Mass Screening; D009154:Mutation; D009394:Nephritis, Hereditary / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D013785:Thailand
chemical_list: D024141:Collagen Type IV