Abstract
Familial hypercholesterolemia (FH) is an autosomal dominant disorder. Although genetic testing is an important tool for detecting FH-causing mutations in patients, diagnostic methods for young patients with severe hypercholesterolemia are understudied. This study compares the target exome sequencing (TES) technique with the DNA resequencing array technique on young patients with severe hypercholesterolemia. A total of 20 unrelated patients (mean age 14.8 years) with total cholesterol > 10 mmol/L were included. 12 patient samples were processed by DNA resequencing array, 14 patient samples were processed by TES, and 6 patient samples were processed by both methods. Functional characterization of novel mutations was performed by flow cytometry. The mutation detection rate (MDR) of DNA resequencing array was 75%, while the MDR of TES was 100%. A total of 27 different mutations in the LDLR were identified, including 3 novel mutations and 8 mutations with previously unknown pathogenicity. Functional characterization of c.673delA, c.1363delC, p.Leu575Phe and p.Leu582Phe variants found that all of them are pathogenic. Additionally, 7 patients were diagnosed with Heterozygous FH (HeFH) in which lipid levels were significantly higher than common HeFH patients. This data indicates that TES is a very efficient tool for genetic diagnosis in young patients with severe hypercholesterolemia.
Highlights
We found that target exome sequencing (TES)-based screenings yields a more accurate genetic diagnosis and we conclude that TES is the more appropriate diagnostic technique for young patients with severe hypercholesterolemia
We determined that target exome sequencing is a powerful tool for genetic diagnosis of young patients with severe hypercholesterolemia
It is remarkable that TES technology showed a higher mutation detection rate than DNA resequencing array while being a faster screening technique for patients with severe hypercholesterolemia
Summary
Because of the high cost of both these methods, alternative DNA resequencing assays have been developed to optimize the detection of FH-causing mutations[7]. Next-generation sequencing has been successfully used to conduct screens for FH-causing mutations[8,9]. We previously showed that target exome sequencing (TES) successfully detected LDLR mutations in a FH patient[10]. The aim of the present study is to compare the TES technique with the DNA resequencing array technique in the genetic diagnosis of young patients with severe hypercholesterolemia. We found that TES-based screenings yields a more accurate genetic diagnosis and we conclude that TES is the more appropriate diagnostic technique for young patients with severe hypercholesterolemia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
