Nephrology Dialysis Transplantation, Vol 14, Issue 3 627-630, Copyright © 1999 by Oxford University Press
R Torra, C Badenas, F Cofan, L Callis, L Perez-Oller and A Darnell
Background. Genetic heterogeneity is a well-known
feature of Alport syndrome (AS). Most families with AS show an X-linked
dominant pattern of inheritance but about 15% of families show an autosomal
inheritance of the disease. Autosomal recessive AS may account for 10% of
the total number of cases and is caused by mutations in the COL4A3 and
COL4A4 genes. The clinical spectrum of this rare disorder has not been well
clarified. Methods. We present two families with AS.
Two affected members of these families have entered end-stage renal disease
(ESRD) in their 30s, and the other three are older than 15 years and have
normal serum creatinine. Four of the five patients have deafness but none
have ocular abnormalities. Two have been transplanted and have not suffered
from anti-GBM antibody nephritis. Men and women are equally affected. We
have performed linkage analysis for chromosome 2 with the following
markers: D2S279, COL4A3/4 DNTR, COL4A4 RFLP Hae III. Results.
We demonstrate that both families, one of them consanguineous,
are linked to the COL4A3/4 locus. Conclusions. We can
conclude that the only significant difference between the X-linked and the
autosomal recessive forms of AS lies in the fact that in the latter females
are as affected as males; thus the idea that autosomal recessive AS causes
ESRD during childhood must be discarded. Other clinical features such as
age of deafness or the presence of post-transplant anti-GBM antibody
nephritis show no differences between the entities. Thus an accurate
familial study is mandatory in patients with AS, as the identification of
the different patterns of inheritance may cause a great difference in
genetic counselling. Linkage analysis is the only effective molecular
diagnosis that can be performed nowadays. Keywords:
Alport syndrome; autosomal recessive; clinical features; COL4A3;
COL4A4; genes; hereditary nephritis; linkage analysis; transplantation
ORIGINAL ARTICLES
Autosomal recessive Alport syndrome: linkage analysis and clinical features in two families
Departments of Nephrology and Genetics, Renal Transplant Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain; Department of Nephrology, Hospital Matrnoinfantil, Valle de Hebron, Barcelona, Spain; Corresponding author address: Servicio de Nefrologia, Hospital Clinic, Villarroel 170, E-08036 Barcelona, Spain
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. S. Jun, S. H. Liu, E. H. Koo, D. V. Do, W. J. Stark, and J. D. Gottsch Microarray Analysis of Gene Expression in Human Donor Corneas Arch Ophthalmol, November 1, 2001; 119(11): 1629 - 1634. [Abstract] [Full Text] [PDF]
|
|