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Complexity of molecular genetics of dyslipidemia in a family highly susceptible to ischemic heart disease
Author(s) -
Jensen H. K.,
Hansen P. S.,
Jensen L. G.,
Kristensen M. J.,
Klausen I. C.,
Kjeldsen M.,
Lemming L.,
Bolund L.,
Gregersen N.,
Færgeman O.
Publication year - 1995
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1995.tb04049.x
Subject(s) - frameshift mutation , genetics , hyperlipidemia , biology , stop codon , exon , ldl receptor , mutation , familial hypercholesterolemia , coding region , gene , medicine , endocrinology , lipoprotein , cholesterol , diabetes mellitus
In a Danish family highly susceptible to ischemic heart disease, hyperlipidemia did not simply cosegregate with a previously undescribed 10 bp deletion in the LDL receptor gene causing heterozygous familial hypercholesterolemia (FH). This mutation, designated as FH DK‐4, deletes 10 nucleotides from ex on 4 coding for the third cysteine‐rich repeat of the ligand‐binding domain. The resulting translational frameshift and stop codon corresponding to amino acid position 181 in the LDL receptor cDNA is predicted to result in a truncated LDL receptor protein. Several family members had hyperlipidemia and early onset of ischemic heart disease not due to the 10 bp deletion, and several family members had unexpectedly high serum lipoprotein(a) contributing to high concentrations of serum LDL cholesterol. The study illustrates important limitations and possibilities of molecular genetic diagnosis.