Comparison of DNA array platform vs DNA sequencing as genetic diagnosis tools for familial hypercholesterolemia.

To the Editor: The report by Blesa et al. (1 ) compares 2 methods, DNA sequencing and DNA arrays [as previously reported by us (2 )], for the genetic diagnosis of familial hypercholesterolemia (FH). Lipochip (Lacer SA), the first DNA array-based commercial platform for the genetic diagnosis of FH, is now available and is funded by the Spanish Health Service. The procedure is as follows: blood samples are shipped to a central laboratory, where DNA is analyzed with the first CE-marked (approved for sale in the European Community) DNA array for in vitro diagnosis in Europe. Samples with a negative result undergo large rearrangement analysis by quantitative fluorescence-based multiplex PCR (3 ). If this analysis is also negative, DNA sequencing is carried out to identify new diseasecausing variations. The results are compiled in a full report that is sent to the patient’s physician. Most of the comments by Blesa et al. on our DNA array refer to an earlier version developed for research only (v1.0) (2 ). The most recent version (v4.0) detects 204 LDLreceptor (LDLR) gene variations and 3 alterations in the apolipoprotein B gene (APOB) that cause FH or familial defective apolipoprotein B. Our DNA array is updated yearly with all new variations identified by DNA sequencing. We are working on a new version that can detect 230 variations, including those most frequent in Spain. Patient selection criteria differed in the 2 studies; those of Blesa et al. (1 ) were based on MedPed s clinical criteria, and ours (2 ) were based on Dutch MedPed s score criteria. With our criteria, 129 FH probands from Table 1. Demographical data between patients with ESRD and control participants.