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Identification of mutations in the α3(IV) and α4(IV) collagen genes in autosomal recessive Alport syndrome

Nature Genetics volume 8, pages 77–82 (1994)Cite this article

Abstract

Alport syndrome (AS) is an hereditary disease of basement membranes characterized by progressive renal failure and deafness. Changes in the glomerular basement membrane (GBM) in AS suggest that the type IV collagen matrix, the major structural component of GBM, is disrupted. We recently isolated the genes for two type IV collagens, α3(IV) and α4(IV), that are encoded head-to-head on human chromosome 2. These chains are abundant in normal GBM but are sometimes absent in AS. We screened for mutations in families in which consanguinity suggested autosomal recessive inheritance. Homozygous mutations were found in α3(IV) in two families and in α4(IV) in two others, demonstrating that these chains are important in the structural integrity of the GBM and that there is an autosomal form of AS in addition to the previously-defined X-linked form.

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Author information

Author notes

  1. Toshio Mochizuki

    Present address: Department of Medicine, Division of Nephrology, Albert Einstein College of Medicine, Ullmann 617, 1300 Morris Park Avenue, Bronx, New York, 10461, USA

  2. Stephen T. Reeders

    Present address: Renal Division, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, 02115, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, Suite 136 BCMM, New Haven, Connecticut, 06536-0812, USA

    Toshio Mochizuki, Mariko Mariyama & Stephen T. Reeders

  2. Departments of Human Genetics and Pediatrics, University Hospital Nijmegen, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands

    Henny H. Lemmink, Cornelis H. Schröder & Hubert J. Smeets

  3. INSERM U192, Tour Lavoisier — 6ème étage, Hôpital Necker — Enfants Malades, 149, rue de Sèvres, 75743, Paris Cedex, 15, France

    Corinne Antignac & Marie-Claire Gubler

  4. Nephrology Unit and Center for Human Genetics, University of Louvain Medical School, Avenue Hippocrate 10, Bruxelles, Belgium

    Yves Pirson & Christine Verellen-Dumoulin

  5. Department of Genetics, Yale University School of Medicine, 295 Congress Avenue, Suite 136 BCMM, New Haven, Connecticut, 06536-0812, USA

    Belinda Chan & Stephen T. Reeders

Authors
  1. Toshio Mochizuki
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Mochizuki, T., Lemmink, H., Mariyama, M. et al. Identification of mutations in the α3(IV) and α4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet 8, 77–82 (1994). https://doi.org/10.1038/ng0994-77

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  • DOI: https://doi.org/10.1038/ng0994-77

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