Relative frequency of mutations causing ornithine transcarbamylase deficiency in 78 families

Approximately 90 different mutations associated with ornithine transcarbamylase (OTC) deficiency are currently known. Thus, the majority represent private mutations. However, some of the mutations seemed to be recurrent. Our laboratories identified apparent deleterious mutations in 78 consecutive families with OTC deficiency by screening all exons and exon/intron borders using single-strand conformational polymorphism (75 families) or sequencing of the entire coding sequence (3 families). Large deletions of one or more exons were found in 8% of families and approximately 10% had small deletions or insertions of 1–5 bases. Splice site mutations were found in 18% of families. Contrary to previous reports, recurrent point mutations seemed to be equally distributed among most CpG dinucleotides rather than show prevalent mutations. No single point mutation had a relative frequency of more than 6.4%. Of the 64 families with nucleotide substitutions, 24 (38%) were G to A with the next most common being C to T (16%) and A to T (11%).