Genetic Analysis of Japanese Children Clinically Diagnosed with Familial Hypercholesterolemia.
Genetic Analysis of Japanese Children Clinically Diagnosed with Familial Hypercholesterolemia.
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DOI：
10.5551/jat.62807
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发表时间：
2022-05-01
影响因子：
4.4
通讯作者：
Dobashi, Kazushige
中科院分区：
文献类型：
--
作者：
Nagahara, Keiko;Nishibukuro, Tsuyoshi;Ogiwara, Yasuko;Ikegawa, Kento;Tada, Hayato;Yamagishi, Masakazu;Kawashiri, Masa-aki;Ochi, Ayako;Toyoda, Junya;Nakano, Yuya;Adachi, Masanori;Mizuno, Katsumi;Hasegawa, Yukihiro;Dobashi, Kazushige
目的：本研究旨在阐明临床诊断为家族性高胆固醇血症（FH）的儿童的基因和脂质谱。方法：对来自29个家庭的33名日本FH患儿（平均年龄9.7±4.2岁）进行了血脂异常相关的21个孟德尔基因测序，包括FH致病基因（LDLR、APOB和pcsk9）和ldl改变基因（APOE、LDLRAP1和abcg5 /8）。结果：ldlr致病性变异15例（45.5%），pcsk9致病性变异1例（3.0%）。在17例无FH致病基因变异的患者中，3例患儿存在ldl改变基因变异、anAPOE变异和2例abcg8变异。致病变异阳性组的平均血清总胆固醇（280 vs 246 mg/dL）、低密度脂蛋白胆固醇（LDL-C, 217 vs 177 mg/dL）和非高密度脂蛋白胆固醇（228 vs 188 mg/dL）水平显著高于变异阴性组。在变异阳性组中，81.3%的患者LDL-C水平≥180 mg/dL，而在变异阴性组中，这一比例为35.3%。与其他ldlr变异的儿童相比，错义变异儿童（尤其是p.l u568val变异）的平均LDL-C水平显著降低，而改变ldl的变异对血清LDL-C toLDLR p.l u568val的升高有相似的影响。结论：在临床诊断为FH的儿童中，约有一半存在FH致病基因的致病性变异。伴有致病性变异的FH患儿血清LDL-C水平较高，且随变异类型不同而不同。基因分析是有用的；然而，需要对无变异的FH进行进一步的研究。
Aim: This study aimed to elucidate the gene and lipid profiles of children clinically diagnosed with familial hypercholesterolemia (FH). Methods: A total of 21 dyslipidemia-related Mendelian genes, including FH causative genes (LDLR,APOB, andPCSK9) and LDL-altering genes (APOE,LDLRAP1, andABCG5/8), were sequenced in 33 Japanese children (mean age, 9.7±4.2 years) with FH from 29 families. Results: Fifteen children (45.5%) with pathogenic variants inLDLR (eight different heterozygous variants) and one child (3.0%) with thePCSK9 variant were found. Among 17 patients without FH causative gene variants, 3 children had variants in LDL-altering genes, anAPOE variant and twoABCG8 variants. The mean serum total cholesterol (280 vs 246 mg/dL), LDL-cholesterol (LDL-C, 217 vs 177 mg/dL), and non-HDL cholesterol (228 vs 188 mg/dL) levels were significantly higher in the pathogenic variant-positive group than in the variant-negative group. In the variant-positive group, 81.3% of patients had LDL-C levels ≥ 180 mg/dL but 35.3% in the variant-negative group. The mean LDL-C level was significantly lower in children with missense variants, especially with the p.Leu568Val variant, than in children with other variants inLDLR, whereas the LDL-altering variants had similar effects on the increase in serum LDL-C toLDLR p.Leu568Val. Conclusion: Approximately half of the children clinically diagnosed with FH had pathogenic variants in FH causative genes. The serum LDL-C levels tend to be high in FH children with pathogenic variations, and the levels are by the types of variants. Genetic analysis is useful; however, further study on FH without any variants is required.
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影响因子：
39.3
作者：
Nordestgaard BG;Chapman MJ;Humphries SE;Ginsberg HN;Masana L;Descamps OS;Wiklund O;Hegele RA;Raal FJ;Defesche JC;Wiegman A;Santos RD;Watts GF;Parhofer KG;Hovingh GK;Kovanen PT;Boileau C;Averna M;Borén J;Bruckert E;Catapano AL;Kuivenhoven JA;Pajukanta P;Ray K;Stalenhoef AF;Stroes E;Taskinen MR;Tybjærg-Hansen A;European Atherosclerosis Society Consensus Panel
通讯作者：
European Atherosclerosis Society Consensus Panel
影响因子：
4.4
作者：
Harada-Shiba M;Ohta T;Ohtake A;Ogura M;Dobashi K;Nohara A;Yamashita S;Yokote K;Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia
通讯作者：
Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia
DOI：
10.1161/circgenetics.114.000776
发表时间：
2015-04
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Stitziel NO;Peloso GM;Abifadel M;Cefalu AB;Fouchier S;Motazacker MM;Tada H;Larach DB;Awan Z;Haller JF;Pullinger CR;Varret M;Rabès JP;Noto D;Tarugi P;Kawashiri MA;Nohara A;Yamagishi M;Risman M;Deo R;Ruel I;Shendure J;Nickerson DA;Wilson JG;Rich SS;Gupta N;Farlow DN;Neale BM;Daly MJ;Kane JP;Freeman MW;Genest J;Rader DJ;Mabuchi H;Kastelein JJ;Hovingh GK;Averna MR;Gabriel S;Boileau C;Kathiresan S
通讯作者：
Kathiresan S
DOI：
10.1073/pnas.84.19.6919
发表时间：
1987-10-01
影响因子：
11.1
作者：
INNERARITY, TL;WEISGRABER, KH;GRUNDY, SM
通讯作者：
GRUNDY, SM
DOI：
10.1161/01.atv.15.10.1713
发表时间：
1995-10-01
影响因子：
8.7
作者：
MARUYAMA, T;MIYAKE, Y;YAMAMOTO, A
通讯作者：
YAMAMOTO, A