Screening for gene deletions and known mutations in 13 patients with ornithine transcarbamylase deficiency

We analyzed DNA from 13 males with ornithine transcarbamylase (OTC) deficiency for gene deletions and known point mutations using the polymerase chain reaction (PCR), allelle-specific oligonucleotide (ASO) hybridization, and Southern blotting with full-length OTC cDNA and exon-specific probes. Three patients were found to have deletions: one was missing the whole OTC gene; a second patient had a deletion of both exon 7 and 8; and the third had a deletion of exon 9. Only one of the remaining 10 patients had a known point mutation consisting of a G-to-A change in nucleotide 422 of the sense strand resulting in a glutamine substitution for arginine at amino acid 109 of the mature OTC protein. This study describes the integration of various molecular methods to screen OTC-deficient patients for deletions and points mutations. Two new deletions within the OTC gene are described.