Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific alterations?
BACKGROUND
Familial hypercholesterolemia (FH) is a frequent form of autosomal-dominant hypercholesterolemia that predisposes to premature coronary atherosclerosis. FH is caused by sequence variations in the gene coding for the LDL receptor (LDLR). This gene has a wide spectrum of sequence variations, and genetic diagnosis can be performed by 2 strategies.


METHODS
Point variations and large rearrangements were screened along all the LDLR gene (promoter, exons, and flanking intron sequences).


RESULTS
We screened a sample of 129 FH probands from the Valencian Community, Spain, and identified 54 different LDLR sequence variations. The most frequent (10% of cases) was 111insA, and 60% of the variants had a frequency as low as 1%. A previously described method for detection of known sequence variations in the Spanish population by DNA array analysis allowed the identification of only approximately 50% of patients with a variant LDLR gene and approximately 40% of the screened samples.


CONCLUSIONS
Our results indicate that the adequate procedure to identify LDLR sequence variations in outbreed populations should include screening of the entire gene.
Blesa
Sebastian
S
Laboratorio de Estudios Genéticos, Fundación de Investigación HCUV, Hospital Clínico Universitario de Valencia, Valencia, Spain.
Garcia-Garcia
Ana Barbara
AB
Martinez-Hervas
Sergio
S
Mansego
Maria Luisa
ML
Gonzalez-Albert
Veronica
V
Ascaso
Juan Francisco
JF
Carmena
Rafael
R
Real
Jose Tomas
JT
Chaves
Felipe Javier
FJ
D001055:Apolipoproteins B / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011973:Receptors, LDL / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013030:Spain
D001055:Apolipoproteins B; D011973:Receptors, LDL