The dibucaine and sil-1 mutations were analyzed by DNA sequencing because their relative proximity enabled them to be coamplified in a single 570-bp product.
In the 52 patients with hereditary hypocholinesterasemia, the most common DNA abnormalities were dibucaine and K-variant mutations: 47 patients carried the dibucaine mutation, whereas 48 were identified with the K-variant (allele frequencies, 0.72 and 0.74 respectively; Tables 3 and 4).
No homozygotes with fluoride or silent mutations were found, and none of the patients had an isolated homozygous dibucaine defect.
In total, 73% of patients with primary hypocholinesterasemia had abnormalities at the dibucaine and K-variant loci only.
This proband was heterozygous for dibucaine and K-variant, hence, compound heterozygous for three mutations (Fig.
Three patients had hypocholinesterasemia with BCHE gene defects: two K-variant homozygotes (patients 6 and 21), and one dibucaine heterozygote (patient 4; shown in the Data Supplement).
The importance of the dibucaine mutation in patients with primary hypocholinesterasemia was undisputable.
The mutation relationship responsible for most compound genotypes was coexpression of dibucaine and K-variant (88% of patients).
Although linkage is well described, the number of dibucaine and K-variant mutations did not always correlate in the genotypes of our patients.
Our referral population was composed of 43% dibucaine homozygotes, 31% dibucaine heterozygotes, 8% silent mutations, 6% fluoride mutations, 12% rare mutations, and 11% with genotypes that could not be resolved.
In conclusion, our work genotyping patients with prolonged post-SC apnea revealed high prevalences of dibucaine and K-variant defects in primary hypocholinesterasemia; therefore, a mutation screening approach was suitable for diagnosis in these individuals.