Sl. Primoparmo et al., CHARACTERIZATION OF 12 SILENT ALLELES OF THE HUMAN BUTYRYLCHOLINESTERASE (BCHE) GENE, American journal of human genetics, 58(1), 1996, pp. 52-64
The silent phenotype of human butyrylcholinesterase (BChE), present in
most human populations in frequencies of similar to 1/100,000, is cha
racterized by the complete absence of BChE activity or by activity <10
% of the average levels of the usual phenotype. Heterogeneity in this
phenotype has been well established at the phenotypic level, but only
a few silent BCHE alleles have been characterized at the DNA level. Tw
elve silent alleles of the human butyrylcholinesterase gene (BCHE) hav
e been identified in 17 apparently unrelated patients who were selecte
d by their increased sensitivity to the muscle relaxant succinylcholin
e. All of these alleles are characterized by single nucleotide substit
utions or deletions leading to distinct changes in the structure of th
e BChE enzyme molecule. Nine of the nucleotide substitutions result in
the replacement of single amino acid residues. Three of these variant
s, BCHE33C, BCHE*198G, and BCHE*-201T, produce normal amounts of immu
noreactive but enzymatically inactive BChE protein in the plasma. The
other six amino acid substitutions, encoded by BCHE37S, BCHE*125F, BC
HE170E, BCHE*471R, and BCHE*518L, seem to cause reduced expression of
BChE protein, and their role in determining the silent phenotype was
confirmed by expression in cell culture. The other four silent alleles
, BCHE271STOP, BCHE*500STOP, BCHE*FS6, and BCHE*I2E3-8G, encode BChEs
truncated at their C-terminus because of premature stop codons caused
by nucleotide substitutions, a frame shift, or altered splicing. The
large number of different silent BCHE alleles found within a relativel
y small number of patients shows that the heterogeneity of the silent
BChE phenotype is high. The characterization of silent BChE variants w
ill be useful in the study of the structure/function relationship for
this and other closely related enzymes.