The major allele of the alanine:glyoxylate aminotransferase gene:: seven novel mutations causing primary hyperoxaluria type 1

We describe 7 novel mutations occurring on the major allele of the human AGT gene in patients with primary hyperoxaluria, type 1, an autosomal recessive disease resulting from a deficiency of the liver peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44). These mutations include 3 small deletions, 570delG, 744delC, and 983_988del, two splice junction mutations, IVS7- IG --> C and IVS8 + IG --> T, and two nonsense mutations, R111X and W251X. We have also identified recurrences of previously identified reported mutations, 679-(IVS6+2)delAAgt, IVS8-3C--> G and 33insC. Deletion mutation 679 - (IVS6 + 2)delAAgt has now been identified in a second Chinese patient and may be specific to that population. In contrast, 33insC has been found in patients of varying ethnic and racial backgrounds; a single vs multiple origin for this mutation is thus an intriguing question. It also appears to occur at a high frequency on the major allele. Five of the novel mutations were detected in patients who were compound heterozygotes for one of the common mis-targeting mutation, G170R or F152I, while the other two mutations occurred in the same patient. (C) 2004 Elsevier Inc. All rights reserved.