Summary
Here, we report the prenatal diagnosis of familial hypercholesterolemia in a Christian-Arab family that carries the “Lebanese” mutation, a single base substitution that creates a HinfI restriction site, at the low density lipoprotein (LDL) receptor locus. Polymerase chain reaction amplification and restriction analysis were performed on genomic DNA extracted from a chorionic villus sample. In conjunction with karyotype analysis, the fetus was identified as a heterozygous female. Analysis of LDL receptor restriction fragment length polymorphisms confirmed the presence of a male parent marker and revealed that the fetus inherited the mutant gene from its mother. This technique offers a simple and rapid diagnostic tool that can be carried out at an early stage of gestation. It is recommended for families and population groups with molecularly defined LDL receptor mutations.
This is a preview of subscription content, log in via an institution to check access.
References
Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232:34–47
Brown MS, Kovanen PT, Goldstein JL, Eeckels R, Vandenberghe K, Berghe HVD, Fryns JP, Cassiman JJ (1978) Prenatal diagnosis of homozygous familial hypercholesterolemia: expression of a genetic receptor disease in utero. Lancet 1:526–529
de-Gennes JL, Daffos F, Dairou F, Forestier F, Capella-Pavlosky M, Truffert J, Gaschard JC, Darbois Y (1985) Direct fetal blood examination for prenatal diagnosis of homozygous familial hypercholesterolemia. Arteriosclerosis 5:440–442
Freundlich E, Hino N (1984) Consanguineous marriage among rural Arabs in Israel. Isr J Med Sci 20:1035–1038
Goldstein JL, Brown MS (1989) Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 1215–1250
Hobbs HH, Brown MS, Goldstein JL, Russell DW (1986) Deletion of exon encoding cysteine-rich repeat of the LDL receptor alters its binding specificity in a subject with familial hypercholesterolemia. J Biol Chem 261:13114–13120
Hobbs HH, Brown MS, Russell DW, Davignon J, Goldstein JL (1987) Deletion in the gene for the low-density lipoprotein receptor in a majority of French Canadians with familial hypercholesterolemia. N Engl J Med 317:734–737
Khachadurian AK, Uthman SB (1973) Experiences with the homozygous cases of familial hypercholesterolemia. Nutr Metab 15:132–140
Lehrman MA, Schneider WJ, Brown MS, Davis CG, Elhammer A, Russel DW, Goldstein JL (1987) The Lebanese allele at the LDL receptor gene locus: nonsense mutation produces truncated receptor that is retained in the endoplasmic reticulum. J Biol Chem 262:401–410
Leitersdorf E, Chakravarti A, Hobbs HH (1989a) Polymorphic DNA haplotypes at the LDL receptor locus. Am J Hum Genet 44:409–421
Leitersdorf E, Westhuyzen DR van der, Goetzee GA, Hobbs HH (1989b) Two common low density lipoprotein gene mutations cause familial hypercholesterolemia in Afrikaners. J Clin Invest 84:954–961
Leitersdorf E, Tobin EJ, Davignon J, Hobbs HH (1990) Common low-density lipoprotein receptor mutation in the French Canadian population. J Clin Invest 85:1014–1023
Meiner V, Landsberger D, Berkman N, Reshef A, Segal P, Seftel HC, Westhuyzen DR van der, Jeenah MS, Coetzee GA, Leitersdorf E (1991) A common Lithuanian mutation causing familial hypercholesterolemia in Ashkenazi Jews. Am J Hum Genet 49:443–449
Oppenheim A, Friedlander Y, Dann EJ, Berkman N, Pressman Schwartz S, Leitersdorf E (1991) Hypercholesterolemia in five Israeli Christian-Arab kindreds is caused by the “Lebanese” allele at the low density lipoprotein receptor gene locus as well as by an additional independent major factor. Hum Genet 88:75–84
Rose V, Wilson G, Steiner G (1982) Familial hypercholesterolemia: report of coronary death at age 3 in a homozygous child and prenatal diagnosis in a heterozygous sibling. J Pediatr 100:757–759
Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Reshef, A., Meiner, V., Dann, E.J. et al. Prenatal diagnosis of familial hypercholesterolemia caused by the “Lebanese” mutation at the low density lipoprotein receptor locus. Hum Genet 89, 237–239 (1992). https://doi.org/10.1007/BF00217130
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00217130