Detection of a single base deletion in codon 424 of the low density lipoprotein receptor gene in a Danish family with familial hypercholesterolemia

TY - JOUR

T1 - Detection of a single base deletion in codon 424 of the low density lipoprotein receptor gene in a Danish family with familial hypercholesterolemia

AU - Nissen, H

AU - Hansen, A B

AU - Guldberg, P

AU - Petersen, N E

AU - Larsen, M L

AU - Haghfelt, T

AU - Kristiansen, K

AU - Hørder, M

N1 - Keywords: Adolescent; Adult; Aged; Amino Acid Sequence; Base Sequence; Child; Child, Preschool; Codon; Denmark; Electrophoresis, Gel, Two-Dimensional; Female; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Molecular Sequence Data; Mutation; Myocardial Ischemia; Pedigree; Polymerase Chain Reaction; Receptors, LDL; Survivors

PY - 1994

Y1 - 1994

N2 - We performed a screening of exon 9 of the low density lipoprotein receptor (LDLR) gene in 14 Danish families with familial hypercholesterolemia (FH) using the denaturing gradient gel electrophoresis (DGGE) technique. In one of the probands from these families an abnormal band pattern in the gradient gel was detected. Subsequent DGGE analysis of the family of this index patient revealed that the DGGE pattern cosegregated with the disease in this family. Sequencing of the exon showed a deletion of a C in codon 424 of the LDLR gene resulting in a frame shift with the introduction of a stop codon 5 codons further downstream. The mutation is referred to as FH-Odense. The predicted truncated receptor protein consists of the 428 amino terminal amino acids. Consequently, the cytosolic and membrane spanning parts of the mature LDL receptor, which normally secure the receptor in the plasma membrane, are missing. The FH-Odense mutation results in severe premature coronary atherosclerosis as shown by the clinical expression in 5 generations of the affected family.

AB - We performed a screening of exon 9 of the low density lipoprotein receptor (LDLR) gene in 14 Danish families with familial hypercholesterolemia (FH) using the denaturing gradient gel electrophoresis (DGGE) technique. In one of the probands from these families an abnormal band pattern in the gradient gel was detected. Subsequent DGGE analysis of the family of this index patient revealed that the DGGE pattern cosegregated with the disease in this family. Sequencing of the exon showed a deletion of a C in codon 424 of the LDLR gene resulting in a frame shift with the introduction of a stop codon 5 codons further downstream. The mutation is referred to as FH-Odense. The predicted truncated receptor protein consists of the 428 amino terminal amino acids. Consequently, the cytosolic and membrane spanning parts of the mature LDL receptor, which normally secure the receptor in the plasma membrane, are missing. The FH-Odense mutation results in severe premature coronary atherosclerosis as shown by the clinical expression in 5 generations of the affected family.

M3 - Journal article

C2 - 7718023

SN - 0021-9150

VL - 111

SP - 209

EP - 215

JO - Atherosclerosis

JF - Atherosclerosis

IS - 2

ER -