PMID- 10205269
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20181113
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 5
DP  - 1999 May
TI  - A third major locus for autosomal dominant hypercholesterolemia maps to
      1p34.1-p32.
PG  - 1378-87
AB  - Autosomal dominant hypercholesterolemia (ADH), one of the most frequent
      hereditary disorders, is characterized by an isolated elevation of LDL particles 
      that leads to premature mortality from cardiovascular complications. It is
      generally assumed that mutations in the LDLR and APOB genes account for ADH. We
      identified one large French pedigree (HC2) and 12 additional white families with 
      ADH in which we excluded linkage to the LDLR and APOB, implicating a new locus we
      named "FH3." A LOD score of 3.13 at a recombination fraction of 0 was obtained at
      markers D1S2892 and D1S2722. We localized the FH3 locus to a 9-cM interval at
      1p34.1-p32. We tested four regional markers in another set of 12 ADH families.
      Positive LOD scores were obtained in three pedigrees, whereas linkage was
      excluded in the others. Heterogeneity tests indicated linkage to FH3 in
      approximately 27% of these non-LDLR/non-APOB ADH families and implied a fourth
      locus. Radiation hybrid mapping located four candidate genes at 1p34.1-p32,
      outside the critical region, showing no identity with FH3. Our results show that 
      ADH is genetically more heterogeneous than conventionally accepted.
FAU - Varret, M
AU  - Varret M
AD  - Hopital Necker-Enfants Malades, Institut National de la Sante et de la Recherche 
      Medicale, Unit 383, Universite Rene Descartes, 75743 Paris Cedex 15, France.
FAU - Rabes, J P
AU  - Rabes JP
FAU - Saint-Jore, B
AU  - Saint-Jore B
FAU - Cenarro, A
AU  - Cenarro A
FAU - Marinoni, J C
AU  - Marinoni JC
FAU - Civeira, F
AU  - Civeira F
FAU - Devillers, M
AU  - Devillers M
FAU - Krempf, M
AU  - Krempf M
FAU - Coulon, M
AU  - Coulon M
FAU - Thiart, R
AU  - Thiart R
FAU - Kotze, M J
AU  - Kotze MJ
FAU - Schmidt, H
AU  - Schmidt H
FAU - Buzzi, J C
AU  - Buzzi JC
FAU - Kostner, G M
AU  - Kostner GM
FAU - Bertolini, S
AU  - Bertolini S
FAU - Pocovi, M
AU  - Pocovi M
FAU - Rosa, A
AU  - Rosa A
FAU - Farnier, M
AU  - Farnier M
FAU - Martinez, M
AU  - Martinez M
FAU - Junien, C
AU  - Junien C
FAU - Boileau, C
AU  - Boileau C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Apolipoproteins B)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Genetic Markers)
RN  - 0 (Receptors, LDL)
SB  - IM
MH  - Adult
MH  - Apolipoproteins B/*genetics
MH  - Cholesterol, LDL
MH  - *Chromosome Mapping
MH  - Chromosomes, Human, Pair 1/*genetics
MH  - Female
MH  - Genetic Markers
MH  - Humans
MH  - Hyperlipoproteinemia Type II/*genetics
MH  - Lod Score
MH  - Pedigree
MH  - Receptors, LDL/*genetics
PMC - PMC1377874
EDAT- 1999/04/17 02:14
MHDA- 2000/03/21 09:00
CRDT- 1999/04/17 02:14
PHST- 1999/04/17 02:14 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/04/17 02:14 [entrez]
AID - S0002-9297(07)62283-6 [pii]
AID - 10.1086/302370 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 May;64(5):1378-87. doi: 10.1086/302370.