Miroshnikova Valentina V, Romanova Olga V, Ivanova Olga N, Fedyakov Mikhail A, Panteleeva Alexandra A, Barbitoff Yury A, Muzalevskaya Maria V, Urazgildeeva Sorejya A, Gurevich Victor S, Urazov Stanislav P, Scherbak Sergey G, Sarana Andrey M, Semenova Natalia A, Anisimova Inga V, Guseva Darya M, Pchelina Sofya N, Glotov Andrey S, Zakharova Ekaterina Y, Glotov Oleg S
Laboratory of Human Molecular Genetics, Molecular and Radiation Biophysics Department, Petersburg Nuclear Physics Institute, National Research Center 'Kurchatov Institute', Gatchina 188300, Russian Federation.
Genetic Laboratory of City Hospital No. 40, Saint-Petersburg, 197706, Russian Federation.
Biomed Rep. 2021 Jan;14(1):15. doi: 10.3892/br.2020.1391. Epub 2020 Nov 17.
Familial hypercholesterolemia (FH) is caused by mutations in various genes, including the , and genes; however, the spectrum of these mutations in Russian individuals has not been fully investigated. In the present study, mutation screening was performed on the gene and other FH-associated genes in patients with definite or possible FH, using next-generation sequencing. In total, 59 unrelated patients were recruited and sorted into two separate groups depending on their age: Adult (n=31; median age, 49; age range, 23-70) and children/adolescent (n=28; median age, 11; age range, 2-21). FH-associated variants were identified in 18 adults and 25 children, demonstrating mutation detection rates of 58 and 89% for the adult and children/adolescent groups, respectively. In the adult group, 13 patients had FH-associated mutations in the gene, including two novel variants [NM_000527.4: c.433_434dupG p.(Val145Glyfs35) and c.1186G>C p.(Gly396Arg)], 3 patients had mutations and two had mutations. In the children/adolescent group, 21 patients had FH-causing mutations in the gene, including five novel variants [NM_000527.4: c.325T>G p.(Cys109Gly), c.401G>C p.(Cys134Ser), c.616A>C p.(Ser206Arg), c.1684_1691delTGGCCCAA p.(Pro563Hisfs14) and c.940+1_c.940+4delGTGA], and 2 patients had mutations, as well as and mutations, being found in different patients. The present study reported seven novel variants considered to be pathogenic or likely pathogenic. Among them, four missense variants were located in the coding regions, which corresponded to functional protein domains, and two frameshifts were identified that produced truncated proteins. These variants were observed only once in different patients, whereas a splicing variant in intron 6 (c.940+1_c.940+4delGTGA) was detected in four unrelated individuals. Previously reported variants in the and genes were observed in 33 patients. The p.(Gly592Glu) variant was detected in 6 patients, representing 10% of the FH cases reported in the present study, thus it may be a major variant present in the Russian population. In conclusion, the present study identified seven novel variants of the gene and broadens the spectrum of mutations in FH-related genes in the Russian Federation.
家族性高胆固醇血症（FH）由多种基因突变引起，包括 、 和 基因；然而，俄罗斯人群中这些突变的谱型尚未得到充分研究。在本研究中，对明确或可能患有FH的患者的 基因及其他FH相关基因进行了突变筛查，采用下一代测序技术。总共招募了59例无亲缘关系的患者，并根据年龄分为两个独立组：成人组（n = 31；中位年龄49岁；年龄范围23 - 70岁）和儿童/青少年组（n = 28；中位年龄11岁；年龄范围2 - 21岁）。在18名成人和25名儿童中鉴定出FH相关变异，成人组和儿童/青少年组的突变检出率分别为58%和89%。在成人组中，13例患者在 基因中有FH相关突变，包括两个新变异[NM_000527.4：c.433_434dupG p.(Val145Glyfs35)和c.1186G>C p.(Gly396Arg)]，3例患者有 突变，2例有 突变。在儿童/青少年组中，21例患者在 基因中有导致FH的突变，包括五个新变异[NM_000527.4：c.325T>G p.(Cys109Gly)、c.401G>C p.(Cys134Ser)、c.616A>C p.(Ser206Arg)、c.1684_1691delTGGCCCAA p.(Pro563Hisfs14)和c.940+1_c.940+4delGTGA]，2例患者有 突变，以及 突变和 突变，分别在不同患者中发现。本研究报告了七个被认为是致病或可能致病的新 变异。其中，四个错义变异位于编码区，对应于功能性蛋白质结构域，鉴定出两个移码突变产生截短蛋白。这些变异在不同患者中仅出现一次，而内含子6中的一个剪接变异（c.940+1_c.940+4delGTGA）在四名无亲缘关系的个体中被检测到。在33例患者中观察到先前报道的 和 基因变异。 p.(Gly592Glu)变异在6例患者中被检测到，占本研究报告的FH病例的10%，因此它可能是俄罗斯人群中存在的主要变异。总之，本研究鉴定出 基因的七个新变异，并拓宽了俄罗斯联邦FH相关基因的突变谱型。
