Mutation detection in Chinese patients with familial hypercholesterolemia

Abstract

BackgroundFamilial hypercholesterolemia (FH) is the first molecularly and clinically characterized genetic disease of lipid metabolism. It is an autosomal dominant disorder with significantly elevated levels of total cholesterol and low density of lipoprotein cholesterol in serum, which would lead to extensive xanthomas and premature coronary heart disease. Mutations in low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 and Apo lipoprotein B-100 (APOB) have been identified to be the underlying cause of this disease.MethodsGenetic testing and reports of the mutations in the Chinese population are still limited. In this study, 11 unrelated Chinese FH families were enrolled to detect the candidate gene variants by DNA direct sequencing.Results and conclusionWe identified 12 mutations (11 in LDLR and one in APOB) in ten FH families. Three novel LDLR mutations (c.516C>A/p.D172E, c.1720C>A/p.R574S and c.760C>T/p.Q254X) were identified and co-segregated with the affected individuals in the families. Our discoveries not only further supports the significant role of LDLR in FH, but also expands the spectrum of LDLR mutations. These new insights will contribute to the genetic diagnosis and counseling of FH patients.

Expanding the genetic spectrum for Chinese familial hypercholesterolemia population with six genetic mutations identified using a next‐generation sequencing‐based laboratory‐developed screening test

“…C.G1879A (p.A627T) and c.G682T (p.E228X) are two common variants that have been reported by a number of studies in China, including Taiwan (Cao et al, 2018 ; Chang, 2003 ; Du et al, 2016 ; Jiang, Sun, et al, 2016 ; Jiang, Wu, et al, 2016 ; Mak et al, 1998 ). Furthermore, c.G682T has also been reported in other Asian countries, such as Korea (Han et al, 2015 ), Russia (Zakharova et al, 2005 ), and others (Reiman et al, 2016 ).…”

Spectrum of low-density lipoprotein receptor (LDLR) mutations in a cohort of Sri Lankan patients with familial hypercholesterolemia – a preliminary report

“…The missense mutation c.1720C > A (p.R574S) in exon 12 detected in another patient was described recently in a 13-year old Chinese boy with FH. This mutation was predicted to be pathogenic using function prediction bioinformatics tools [ 31 ]. However, this mutation is not listed in any of the human genome variant databases.…”