Genetic testing of Korean Familial hypercholesterolemia using whole-exome sequencing

Soo Min Han, Byungjin Hwang, Tae Gun Park, Do Il Kim, Moo Yong Rhee, Byoung Kwon Lee, Young Keun Ahn, Byung Ryul Cho, Jeongtaek Woo, Seung Ho Hur, Jin Ok Jeong, Sungha Park, Yangsoo Jang, Min Goo Lee, Duhee Bang, Ji Hyun Lee, Sang Hak Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk of earlyonset coronary artery disease. Although some clinically diagnosed FH cases are caused by mutations in LDLR, APOB, or PCSK9, mutation detection rates and profiles can vary across ethnic groups. In this study, we aimed to provide insight into the spectrum of FH-causing mutations in Koreans. Among 136 patients referred for FH, 69 who met Simon Broome criteria with definite family history were enrolled. By whole-exome sequencing (WES) analysis, we confirmed that the 3 known FH-related genes accounted for genetic causes in 23 patients (33.3%). A substantial portion of the mutations (19 of 23 patients, 82.6%) resulted from 17 mutations and 2 copy number deletions in LDLR gene. Two mutations each in the APOB and PCSK9 genes were verified. Of these anomalies, two frameshift deletions in LDLR and one mutation in PCSK9were identified as novel causative mutations. In particular, one novel mutation and copy number deletion were validated by co-segregation in their relatives. This study confirmed the utility of genetic diagnosis of FH through WES.

Original languageEnglish
Article numbere0126706
JournalPloS one
Volume10
Issue number5
DOIs
Publication statusPublished - 2015 May 11

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Exome
Hyperlipoproteinemia Type II
hypercholesterolemia
Genetic Testing
Genes
mutation
Mutation
Testing
testing
Inborn Genetic Diseases
cultural heritage
Mutation Rate
gene deletion
Ethnic Groups
genetic disorders
nationalities and ethnic groups
Coronary Artery Disease
genes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Han, S. M., Hwang, B., Park, T. G., Kim, D. I., Rhee, M. Y., Lee, B. K., ... Lee, S. H. (2015). Genetic testing of Korean Familial hypercholesterolemia using whole-exome sequencing. PloS one, 10(5), [e0126706]. https://doi.org/10.1371/journal.pone.0126706
Han, Soo Min ; Hwang, Byungjin ; Park, Tae Gun ; Kim, Do Il ; Rhee, Moo Yong ; Lee, Byoung Kwon ; Ahn, Young Keun ; Cho, Byung Ryul ; Woo, Jeongtaek ; Hur, Seung Ho ; Jeong, Jin Ok ; Park, Sungha ; Jang, Yangsoo ; Lee, Min Goo ; Bang, Duhee ; Lee, Ji Hyun ; Lee, Sang Hak. / Genetic testing of Korean Familial hypercholesterolemia using whole-exome sequencing. In: PloS one. 2015 ; Vol. 10, No. 5.
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abstract = "Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk of earlyonset coronary artery disease. Although some clinically diagnosed FH cases are caused by mutations in LDLR, APOB, or PCSK9, mutation detection rates and profiles can vary across ethnic groups. In this study, we aimed to provide insight into the spectrum of FH-causing mutations in Koreans. Among 136 patients referred for FH, 69 who met Simon Broome criteria with definite family history were enrolled. By whole-exome sequencing (WES) analysis, we confirmed that the 3 known FH-related genes accounted for genetic causes in 23 patients (33.3{\%}). A substantial portion of the mutations (19 of 23 patients, 82.6{\%}) resulted from 17 mutations and 2 copy number deletions in LDLR gene. Two mutations each in the APOB and PCSK9 genes were verified. Of these anomalies, two frameshift deletions in LDLR and one mutation in PCSK9were identified as novel causative mutations. In particular, one novel mutation and copy number deletion were validated by co-segregation in their relatives. This study confirmed the utility of genetic diagnosis of FH through WES.",
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Han, SM, Hwang, B, Park, TG, Kim, DI, Rhee, MY, Lee, BK, Ahn, YK, Cho, BR, Woo, J, Hur, SH, Jeong, JO, Park, S, Jang, Y, Lee, MG, Bang, D, Lee, JH & Lee, SH 2015, 'Genetic testing of Korean Familial hypercholesterolemia using whole-exome sequencing', PloS one, vol. 10, no. 5, e0126706. https://doi.org/10.1371/journal.pone.0126706

Genetic testing of Korean Familial hypercholesterolemia using whole-exome sequencing. / Han, Soo Min; Hwang, Byungjin; Park, Tae Gun; Kim, Do Il; Rhee, Moo Yong; Lee, Byoung Kwon; Ahn, Young Keun; Cho, Byung Ryul; Woo, Jeongtaek; Hur, Seung Ho; Jeong, Jin Ok; Park, Sungha; Jang, Yangsoo; Lee, Min Goo; Bang, Duhee; Lee, Ji Hyun; Lee, Sang Hak.

In: PloS one, Vol. 10, No. 5, e0126706, 11.05.2015.

Research output: Contribution to journalArticle

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T1 - Genetic testing of Korean Familial hypercholesterolemia using whole-exome sequencing

AU - Han, Soo Min

AU - Hwang, Byungjin

AU - Park, Tae Gun

AU - Kim, Do Il

AU - Rhee, Moo Yong

AU - Lee, Byoung Kwon

AU - Ahn, Young Keun

AU - Cho, Byung Ryul

AU - Woo, Jeongtaek

AU - Hur, Seung Ho

AU - Jeong, Jin Ok

AU - Park, Sungha

AU - Jang, Yangsoo

AU - Lee, Min Goo

AU - Bang, Duhee

AU - Lee, Ji Hyun

AU - Lee, Sang Hak

PY - 2015/5/11

Y1 - 2015/5/11

N2 - Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk of earlyonset coronary artery disease. Although some clinically diagnosed FH cases are caused by mutations in LDLR, APOB, or PCSK9, mutation detection rates and profiles can vary across ethnic groups. In this study, we aimed to provide insight into the spectrum of FH-causing mutations in Koreans. Among 136 patients referred for FH, 69 who met Simon Broome criteria with definite family history were enrolled. By whole-exome sequencing (WES) analysis, we confirmed that the 3 known FH-related genes accounted for genetic causes in 23 patients (33.3%). A substantial portion of the mutations (19 of 23 patients, 82.6%) resulted from 17 mutations and 2 copy number deletions in LDLR gene. Two mutations each in the APOB and PCSK9 genes were verified. Of these anomalies, two frameshift deletions in LDLR and one mutation in PCSK9were identified as novel causative mutations. In particular, one novel mutation and copy number deletion were validated by co-segregation in their relatives. This study confirmed the utility of genetic diagnosis of FH through WES.

AB - Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk of earlyonset coronary artery disease. Although some clinically diagnosed FH cases are caused by mutations in LDLR, APOB, or PCSK9, mutation detection rates and profiles can vary across ethnic groups. In this study, we aimed to provide insight into the spectrum of FH-causing mutations in Koreans. Among 136 patients referred for FH, 69 who met Simon Broome criteria with definite family history were enrolled. By whole-exome sequencing (WES) analysis, we confirmed that the 3 known FH-related genes accounted for genetic causes in 23 patients (33.3%). A substantial portion of the mutations (19 of 23 patients, 82.6%) resulted from 17 mutations and 2 copy number deletions in LDLR gene. Two mutations each in the APOB and PCSK9 genes were verified. Of these anomalies, two frameshift deletions in LDLR and one mutation in PCSK9were identified as novel causative mutations. In particular, one novel mutation and copy number deletion were validated by co-segregation in their relatives. This study confirmed the utility of genetic diagnosis of FH through WES.

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