Rong Xiang1, Liang-Liang Fan2, Min-Jie Lin3, Jing-Jing Li2, Xiang-Yu Shi3, Jie-Yuan Jin2, Yu-Xing Liu2, Ya-Qin Chen3, Kun Xia4, Shui-Ping Zhao5. 1. The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha 410013, China; Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, 410011, China. Electronic address: shirlesmile@csu.edu.cn. 2. The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha 410013, China. 3. Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, 410011, China. 4. The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha 410013, China. Electronic address: xiakun@sklmg.edu.cn. 5. Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, 410011, China. Electronic address: zhaosp@medmail.com.cn.
Abstract
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is the most common and severe autosomal dominant lipid metabolism dysfunction, which causes xanthoma, atherosclerosis and coronary heart disease. Earlier studies showed that mutations in LDLR, APOB and PCSK9 cause FH. Although more than 75% of the population in Europe has been scrutinized for FH-causing mutations, the genetic diagnosis proportion among Chinese people remains very low (less than 0.5%). The aim of this study was to perform a survey and mutation detection among the Chinese population. METHODS: 219 FH patients from the central south region of China were enrolled. After extracting DNA from circulating lymphocytes, we used direct DNA sequencing to screen each exon of LDLR, APOB and PCSK9. All detected variants were predicted by Mutationtaster, Polyphen-2 and SIFT to assess their effects. RESULTS: In total, 43 mutations were identified from 158 FH patients. Among them, 11 novel mutations were found, including seven LDLR mutations, two APOB mutations and two PCSK9 mutations. Moreover, five common mutations in LDLR were detected. We geographically marked their distributions on the map of China. CONCLUSIONS: The spectrum of FH-causing mutations in the Chinese population is refined and expanded. Along with future studies, our study provides the necessary data as the foundation for the characterization of the allele frequency distribution in the Chinese population. The identification of more LDLR, APOB and PCSK9 novel mutations may expand the spectrum of FH-causing mutations and contribute to the genetic diagnosis and counseling of FH patients.
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is the most common and severe autosomal dominant lipid metabolism dysfunction, which causes xanthoma, atherosclerosis and coronary heart disease. Earlier studies showed that mutations in LDLR, APOB and PCSK9 cause FH. Although more than 75% of the population in Europe has been scrutinized for FH-causing mutations, the genetic diagnosis proportion among Chinese people remains very low (less than 0.5%). The aim of this study was to perform a survey and mutation detection among the Chinese population. METHODS: 219 FHpatients from the central south region of China were enrolled. After extracting DNA from circulating lymphocytes, we used direct DNA sequencing to screen each exon of LDLR, APOB and PCSK9. All detected variants were predicted by Mutationtaster, Polyphen-2 and SIFT to assess their effects. RESULTS: In total, 43 mutations were identified from 158 FHpatients. Among them, 11 novel mutations were found, including seven LDLR mutations, two APOB mutations and two PCSK9 mutations. Moreover, five common mutations in LDLR were detected. We geographically marked their distributions on the map of China. CONCLUSIONS: The spectrum of FH-causing mutations in the Chinese population is refined and expanded. Along with future studies, our study provides the necessary data as the foundation for the characterization of the allele frequency distribution in the Chinese population. The identification of more LDLR, APOB and PCSK9 novel mutations may expand the spectrum of FH-causing mutations and contribute to the genetic diagnosis and counseling of FHpatients.
Authors: Pradeep Natarajan; Gina M Peloso; Seyedeh Maryam Zekavat; May Montasser; Andrea Ganna; Mark Chaffin; Amit V Khera; Wei Zhou; Jonathan M Bloom; Jesse M Engreitz; Jason Ernst; Jeffrey R O'Connell; Sanni E Ruotsalainen; Maris Alver; Ani Manichaikul; W Craig Johnson; James A Perry; Timothy Poterba; Cotton Seed; Ida L Surakka; Tonu Esko; Samuli Ripatti; Veikko Salomaa; Adolfo Correa; Ramachandran S Vasan; Manolis Kellis; Benjamin M Neale; Eric S Lander; Goncalo Abecasis; Braxton Mitchell; Stephen S Rich; James G Wilson; L Adrienne Cupples; Jerome I Rotter; Cristen J Willer; Sekar Kathiresan Journal: Nat Commun Date: 2018-08-23 Impact factor: 17.694
Authors: Khalid Khalaf Alharbi; May Salem Alnbaheen; Fawiziah Khalaf Alharbi; Rana M Hasanato; Imran Ali Khan Journal: Ann Saudi Med Date: 2017 Nov-Dec Impact factor: 1.526