PMID- 10422803
OWN - NLM
STAT- MEDLINE
DCOM- 19990824
LR  - 20190816
IS  - 0009-9163 (Print)
IS  - 0009-9163 (Linking)
VI  - 55
IP  - 5
DP  - 1999 May
TI  - An individual with a healthy phenotype in spite of a pathogenic LDL receptor
      mutation (C240F).
PG  - 332-9
AB  - Familial hypercholesterolemia (FH) is caused by a defect in the function of the
      low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant 
      way. In this study we present a 13-year-old girl, compound heterozygote for the
      LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very 
      low cholesterol esterification rate, LDL uptake, and degradation compared to
      normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was
      expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by
      immunoblotting demonstrated delayed processing of the mutated LDL receptor, which
      was accumulated as a precursor protein of normal size. A high molecular weight
      form of the receptor was also detectable in these cells, which probably reflects 
      cross-linking through the unpaired cysteine residue in the binding domain. Cells 
      expressing the C240F mutant protein were unable to mediate uptake and degradation
      of LDL. The two siblings of the index case also carried the C240F mutation, but
      surprisingly one of them (a 17-year-old brother) showed no signs of
      hypercholesterolemia. This observation is consistent with the view that there may
      be cholesterol lowering mechanisms that can be activated, perhaps by mutations in
      known or hitherto unknown genes.
FAU - Ekstrom, U
AU  - Ekstrom U
AD  - Institute of Laboratory Medicine, Department of Clinical Chemistry, Lund
      University Hospital, Sweden. ulf.ekstrom@klinkem.lu.se
FAU - Abrahamson, M
AU  - Abrahamson M
FAU - Floren, C H
AU  - Floren CH
FAU - Tollig, H
AU  - Tollig H
FAU - Wettrell, G
AU  - Wettrell G
FAU - Nilsson, G
AU  - Nilsson G
FAU - Sun, X M
AU  - Sun XM
FAU - Soutar, A K
AU  - Soutar AK
FAU - Nilsson-Ehle, P
AU  - Nilsson-Ehle P
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - Clin Genet
JT  - Clinical genetics
JID - 0253664
RN  - 0 (DNA, Complementary)
RN  - 0 (Receptors, LDL)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Base Sequence
MH  - CHO Cells
MH  - Child
MH  - Child, Preschool
MH  - Cricetinae
MH  - DNA, Complementary
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Pedigree
MH  - Phenotype
MH  - Receptors, LDL/*genetics
EDAT- 1999/07/28 00:00
MHDA- 1999/07/28 00:01
CRDT- 1999/07/28 00:00
PHST- 1999/07/28 00:00 [pubmed]
PHST- 1999/07/28 00:01 [medline]
PHST- 1999/07/28 00:00 [entrez]
AID - 10.1034/j.1399-0004.1999.550506.x [doi]
PST - ppublish
SO  - Clin Genet. 1999 May;55(5):332-9. doi: 10.1034/j.1399-0004.1999.550506.x.