Clinical Investigation

Kidney International (1992) 42, 1178–1183; doi:10.1038/ki.1992.402

Alport syndrome and diffuse leiomyomatosis: Deletions in the 5' end of the COL4A5 collagen gene

Corinne Antignac, Jing Zhou, Marek Sanak, Pierre Cochat, Bernard Roussel, Georges Deschênes, Françoise Gros, Bertrand Knebelmann, Marie-Claude Hors-Cayla, Karl Tryggvason and Marie-Claire Gubler

INSERM U192 and INSERM U12, Hôpital Necker-Enfants Malades, Paris, France; Biocenter and Department of Biochemistry, University of Oulu, Oulu, Finland; and Unité de Néphrologie Pédiatrique, Hôpital Edouard Herriot, Lyon, Clinique de Pédiatrie et de Puériculture, American Memorial Hospital, Reims, and Service de Néphrologie Pédiatrique, Hôpital de Clocheville, Tours, France

Correspondence: Corinne Antignac MD, INSERM U192, Tour Lavoisier, Hôpital Necker Enfants-Malades, 149 rue de Sèvres, 75015 Paris, France.

Received 24 February 1992; Revised 19 June 1992; Accepted 22 June 1992.

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Abstract

Alport syndrome and diffuse leiomyomatosis: Deletions in the 5' end of the COL4A5 collagen gene. Alport syndrome (AS) is an hereditary glomerulonephritis that is mainly inherited as a dominant X-linked trait. Structural abnormalities in the type IV collagen alpha5 chain gene (COL4A5), which maps to Xq22, have recently been detected in several patients with AS. The association of AS with diffuse esophageal leiomyomatosis (DL) has been reported in 24 patients, most of them also suffering from congenital cataract. The mode of transmission and the location of the gene(s) involved in this association have not been elucidated. Southern blotting using cDNA probes spanning the whole COL4A5 and a 5' end COL4A5 genomic probe showed that three out of three patients with the DL-AS association had a deletion in the 5' part of the COL4A5 gene extending beyond its 5' end. This indicates that the same gene, COL4A5, is involved in classical AS and in DL-AS and that the transmission of DL-AS is X-linked dominant. These results also suggest that leiomyomatosis might be due to the alteration of a second gene involved in smooth muscle cell proliferation, which is located upstream of the COL4A5 gene, and that there might be a contiguous gene deletion syndrome, involving at least the genes coding for congenital cataract, DL and AS.

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