Genetic diagnosis of familial hypercholesterolemia in affected relatives using pedigree tracing.
OBJECTIVE
To describe a process of diagnosing familial hypercholesterolemia (FH) at the DNA level in selected family members of affected individuals.


METHODS
A 63-year-old male patient presented with cholesterol elevations consistent with heterozygous familial hypercholesterolemia. Through participation with the international "MEDPED FH" project to detect affected relatives and to identify their LDL-receptor mutation, the patient was discovered to carry the Lebanese mutation, whereby the codon for cysteine at residue 660 instead codes for a premature termination (C660X), thus truncating the protein product. This mutation also created a new restriction recognition site for the endonuclease Hinfl, which permitted rapid detection of the mutation in selected family members using restriction fragment-length polymorphisms.


RESULTS
The patient's son, who had cholesterol levels consistent with heterozygous FH, was also found to be a heterozygote for the C660X variant of the LDL-receptor.


CONCLUSIONS
Diagnosis of familial hypercholesterolemia at the DNA level is possible as a relatively rapid screening technique in families with a known LDL-receptor mutation, established through participation with the MED-PED FH project.
Hsia
S H
SH
Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.
Connelly
P W
PW
Hegele
R A
RA
D005260:Female; D005820:Genetic Testing; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011973:Receptors, LDL / Q000235:genetics; D015183:Restriction Mapping
D011973:Receptors, LDL