Mutational spectrum in the LDL receptor gene

About 350mutations have been recorded in the
LDL receptor gene (Varret et al., 1998). Of these,
63% are missense mutations. Mutations occur
in all parts of the gene, but there is a relative
excess of mutations in exons 4 and 9. Exons 13
and 15 are involved less often than expected. A
high proportion of mutations (74%) located in
the ligand-binding domain (exons 2–6) involve
amino acids conserved in evolution. (Varret et
al., 1998; data also accessible at
http://www.umd.necker.fr). In addition to point
mutations, several deletions of various sizes
and locations, and insertions have been described.
Depending on the intragenic location of
a mutation, different effects can be observed,
including absent mRNA synthesis, defective intracellular
transport due to abolished binding
(1) or receptor recycling (2), reduced membrane
anchorage (4), and defective internalization
(5). Alu repeats may be involved as a cause
of intragenic deletions.