Identification of deletions and duplications in the low density lipoprotein receptor gene by MLPA.
BACKGROUND
Familial hypercholesterolemia (FH) is caused by mutations in the low density lipoprotein (LDL) receptor gene. In this study we have compared multiplex ligation-dependent probe amplification (MLPA) and long-range PCR to detect large deletions/duplications in the LDL receptor gene.


METHODS
DNA from 431 unrelated FH patients without mutations in the LDL receptor gene detectable by DNA sequencing and who had total serum cholesterol levels above 10.0 mmol/l, was subjected to analyses by MLPA and by five long-range PCRs.


RESULTS
Eleven deletions and two duplications were detected by MLPA. Six of the deletions and one of the duplications were also detected by long-range PCR. A total of 44 of the 431 (10.2%) FH patients possessed a deletion or a duplication.


CONCLUSIONS
MLPA has a higher sensitivity than five long-range PCRs to detect large deletions/duplications in the LDL receptor gene. Even though the direct cost of MLPA is twice that of five long-range PCRs, it has replaced long-range PCR for routine diagnostics in our laboratory because of the higher sensitivity and the 30-50% reduction in hands-on time.
Holla
Øystein  L
Ø
Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet, N-0027 Oslo, Norway.
Teie
Christél
C
Berge
Knut Erik
KE
Leren
Trond P
TP
D000328:Adult; D000368:Aged; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics*; D012680:Sensitivity and Specificity
D011973:Receptors, LDL