[Collagen alpha5 and alpha2 (IV) chain coexpression: The procedure of choice to diagnose Alport syndrome from skin biopsies].
We describe a simple procedure to use skin biopsies for the diagnosis of Alport syndrome. The technique is based on the co-detection of alpha5 and alpha2 chains of collagen IV along the basal lamina of epidermis through an immunfluorescence technique. Eighty-five per cent of the cases of Alport syndrome are due to a mutation in the gene COL4A5, located on chromosome X, encoding the alpha5 chain of collagen IV. In this situation, the tissue expression of alpha5 chain is abnormal; in males, the absence of expression of alpha5 chain is pathognomonic for Alport syndrome; in females, the expression of alpha5 chain may be discontinuous because of X inactivation. The alpha2 chain is used as a positive control. We have studied skin biopsies from 55 patients (35 females, 20 males) with a suspicion of Alport syndrome, along with five controls. Immunofluorescence was performed on frozen tissue samples; for lecture, epifluorescence and confocal microscopy were compared. In controls, both chains were co-detected. In nine males out of 20, the expression of alpha5 was undetectable; it was preserved in the remaining cases. In female patients, the expression was discontinuous in 16 cases and undetectable in one. There was no difference in sensitivity between the two microscopic techniques. The co-detection of alpha5 and alpha2 chains of collagen IV in frozen skin biopsies is therefore proposed as a simple technique to diagnose Alport syndrome, but requires a good knowledge of the conditions of interpretation.
Patey-Mariaud de Serre
Natacha
N
Service d'anatomie pathologique et tumorothèque, hôpital Necker-Enfants malades, université Paris René-Descartes, 149 rue de Sèvres, 75743 Paris cedex 15, France. natacha.patey-mariaud@nck.aphp.fr
Noël
Laure-Hélène
LH
D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009394:Nephritis, Hereditary / Q000235:genetics / Q000473:pathology*; D012867:Skin / Q000473:pathology*
C478159:COL4A5 protein, human; D024141:Collagen Type IV