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Science 8 June 1990:
Vol. 248. no. 4960, pp. 1224 - 1227
DOI: 10.1126/science.2349482
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Articles

Science, Vol 248, Issue 4960, 1224-1227
Copyright © 1990 by American Association for the Advancement of Science

articles

Identification of mutations in the COL4A5 collagen gene in Alport syndrome

DF Barker, SL Hostikka, J Zhou, LT Chow, AR Oliphant, SC Gerken, MC Gregory, MH Skolnick, CL Atkin, and K Tryggvason

Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City 84132.

X-linked Alport syndrome is a hereditary glomerulonephritis in which progressive loss of kidney function is often accompanied by progressive loss of hearing. Ultrastructural defects in glomerular basement membranes (GBM) of Alport syndrome patients implicate an altered structural protein as the cause of nephritis. The product of COL4A5, the alpha 5(IV) collagen chain, is a specific component of GBM within the kidney, and the gene maps to the same X chromosomal region as does Alport syndrome. Three structural aberrations were found in COL4A5, in intragenic deletion, a Pst I site variant, and an uncharacterized abnormality, which appear to cause nephritis and deafness, with allele-specific severity, in three Alport syndrome kindreds in Utah.


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