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Clinical and molecular characteristics of a family with familial hypercholesterolemia with LDLRAP1 and ABCG8 gene abnormality / 中华检验医学杂志
Article em Zh | WPRIM | ID: wpr-934363
Biblioteca responsável: WPRO
ABSTRACT

Objective:

To study the clinical and molecular characteristics of a family with familial hypercholesterolemia (FH) with LDLRAP1 and ABCG8 gene abnormality.

Methods:

In September 2020, one case of FH was included in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; peripheral venous blood samples of members of the family were collected to detect serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) indicators; use high-performance liquid chromatography to detect serum stigmasterol and sitosterol content; perform second-generation gene sequencing to detect gene mutations in probands and family members; use Pymol software to detect gene mutations point for pathogenicity analysis, and use Uniprot Modelling software to perform protein structure modeling.

Results:

The patient presented with anemia, multiple xanthomas and early-onset acute coronary syndrome. The coronary angiography showed severe coronary artery lesions; abdominal ultrasound showed splenomegaly; blood smear showed shaped erythrocytes and large platelets. The level of serum TC, LDL-C, stigmasterol and sitosterol was 8.54 mmol/L (2.3-5.7 mmol/L), 4.84 mmol/L (range of normal value 1.3-4.3 mmol/L), 44 μmol/L (1.0-10 μmol/L), 28 μmol/L (1.0-15 μmol/L), respectively; LDLRAP1 gene mutation was found exon4 c.415C>Tp.Q139X; the truncated protein formed by this homozygous mutation lost multiple stable protein structure regions, which can not have a normal function. At the same time, ABCG8 gene mutations were also found exon13 c.1895T>C (p.V632A) and exon8 c.1199C>Ap.T400K . Two cases of family members had a mild increase in HDL-C (Ⅱ5 2.33 mmol/L, Ⅱ6∶2.96 mmol/L), 3 cases carrying the ABCG8 gene mutations had a slight increase in stigmasterol (Ⅱ8 23 μmol/L, Ⅱ7 24 μmol/L, Ⅰ2 18 μmol/L) and sitosterol (Ⅱ8 41 μmol/L, Ⅱ7 33 μmol/L, Ⅰ2 45 μmol/L), suggesting that its association with the concentration of plant sterols.

Conclusions:

FH patients with LDLRAP1 and ABCG8 gene abnormalities may have abnormal plant sterol concentrations, and their clinical manifestations are more complicated. Therefore, family history, LDL-C, plant sterol levels, and genetic test results should be considered comprehensively.
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Texto completo: 1 Base de dados: WPRIM Tipo de estudo: Prognostic_studies Idioma: Zh Revista: Chinese Journal of Laboratory Medicine Ano de publicação: 2022 Tipo de documento: Article
Texto completo: 1 Base de dados: WPRIM Tipo de estudo: Prognostic_studies Idioma: Zh Revista: Chinese Journal of Laboratory Medicine Ano de publicação: 2022 Tipo de documento: Article