COMPLEXITY OF MOLECULAR-GENETICS OF DYSLIPIDEMIA IN A FAMILY HIGHLY SUSCEPTIBLE TO ISCHEMIC-HEART-DISEASE

In a Danish family highly susceptible to ischemic heart disease, hyper lipidemia did not simply cosegregate with a previously undescribed 10 bp deletion in the LDL receptor gene causing heterozygous familial hyp ercholesterolemia (FH). This mutation, designated as FH DK-4, deletes 10 nucleotides from exon 4 coding for the third cysteine-rich repeat o f the ligand-binding domain. The resulting translational frameshift an d stop codon corresponding to amino acid position 181 in the LDL recep tor cDNA is predicted to result in a truncated LDL receptor protein. S everal family members had hyperlipidemia and early onset of ischemic h eart disease not due to the 10 bp deletion, and several family members had unexpectedly high serum lipoprotein(a) contributing to high conce ntrations of serum LDL cholesterol. The study illustrates important li mitations and possibilities of molecular genetic diagnosis.