Over 300 mutations in the OTC gene have been identified in
patients, with the majority being single base alterations
that alter the amino acid code.
Most families have "private" mutations, with recurrent
mutations typically found at CpG dinucleotides.
CpG dinucleotides tend to
be mutation hotspots.
The maximum number of single base polymorphisms using the
OTC mRNA sequence to be close to 3195, obtained by summing
the possible changes for each codon by only changing one
base at a time (3*3*355 codons). Of these, 152 result in a
mutation that causes a stop codon (TGA, TAA,TAG), 740 of
these changes do not affect the amino acid code (synonymous
mutations; ie: CCT, CCC, CCA, CCG all code for proline),
and 2303 result in changes that affect the amino acid
sequence (nonsynonymous mutations). This analysis does not
correctly account for mutations at the splice junctions, or
for mutations that may affect cryptic splice sites but
provides an approximate estimate of the diversity of
mutations.