Discordant phenotypic expression of Alport syndrome in monozygotic twins.
BACKGROUND
Alport syndrome is a genetically heterogeneous disorder, but most patients showed the X-linked form resulting from mutations in the COL4A5 gene. A few cases of mosaicism in Alport syndrome have been reported.


METHODS
We describe the case of an 8-year-old boy with mosaicism in Alport syndrome. Punch skin biopsies were obtained from the patient's mother and monozygotic twin brother. Five biopsy specimens from non-Alport patients were used as controls. Immunohistochemical analysis was performed using rat monoclonal antibodies towards individual collagen IV(NC) domains.


RESULTS
Kidney tissue of the patient showed: mosaic expression of alpha3(IV), alpha4(IV) and alpha5(IV) in the glomerular basement membrane (GBM), distal tubular basement membrane (TBM) and Bowman's capsule; mosaic alpha6(IV) expression in the Bowman's capsule and distal TBM; and well-preserved expression of alpha1(IV) and alpha2(IV). The patient's skin exhibited mosaic alpha5(IV) expression. His mother and monozygotic twin brother disclosed a normal linear staining of alpha5(IV) in their epidermal basement membranes. This unusual mosaicism of alpha3(IV), alpha4(IV), alpha5(IV) and alpha6(IV) is consistent with a pattern of female heterozygotes of Alport syndrome.


CONCLUSIONS
This discordant phenotypic expression of Alport syndrome in monozygotic twins with unaffected parents suggests possible somatic mosaicism in the COL4A5 gene.
Matsukura
H
H
Department of Pediatrics, Saiseikai Toyama Hospital, Japan. stingray19659@hotmail.com
Higuchi
A
A
Ieki
A
A
Miyawaki
T
T
D002648:Child; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D009030:Mosaicism; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D014430:Twins, Monozygotic
C478159:COL4A5 protein, human; D024141:Collagen Type IV