Three Novel Deletions in the Alanine:Glyoxylate Aminotransferase Gene of Three Patients with Type 1 Hyperoxaluria

We describe three novel deletions in the human AGT gene in three 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). A deletion of 4 nucleotides in the exon 6/intron 6 splice junction (679-IVS6+2delAAgt) is expected to cause missplicing. It would also code for a K227E missense alteration in any mRNA successfully spliced. A 2-bp deletion in exon 11 (1125–1126del CG, cDNA) results in a frameshift. A deletion of at least 5–6 kb, EX1EX5del, spanned exons 1–5 and contiguous upstream sequence. All three deletions are heterozygous with previously documented missense mutations; the intron 6 deletion with F152I, the exon 11 deletion with G82E, and EX1EX5del with the common mistargeting mutation, G170R.