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Updated: Aug 4, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific
Sebastian Blesa1, Ana Barbara Garcia-Garcia, Sergio Martinez-Hervas
1Laboratorio de Estudios Genéticos, Fundación de Investigación HCUV, Hospital Clínico Universitario de Valencia, Valencia, Spain.
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.
Conclusion:
Our results indicate that the adequate procedure to identify LDLR sequence variations in outbreed populations should include screening of the entire gene.
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