The molecular mechanism of Gaucher disease caused by compound heterozygous mutations in GBA1 gene.
The molecular mechanism of Gaucher disease caused by compound heterozygous mutations in GBA1 gene.
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DOI：
10.3389/fped.2023.1092645
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发表时间：
2023
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
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作者：
戈谢病（GD，ORPHA355）是一种罕见的常染色体隐性遗传病，由GBA 1突变引起，GBA 1编码溶酶体酶葡萄糖脑苷脂酶（GCase）。在这里，我们报告了一个GD患者谁携带杂合c.1240G > C（p.Val414Leu）突变和杂合致病性c.1342G > C（p.Asp448His）突变GBA 1。生物信息学分析表明这两个突变都是致病性的。功能研究表明，突变型GBA 1 mRNA和GCase蛋白水平均显著低于野生型。在细胞裂解物中，GBA1 c.1240G > C和c.1342G > C的两个突变导致GCase浓度降低，而这两个突变没有改变细胞中的分布。证实了复合杂合突变的致病性。早期诊断和治疗可以提高GD患者的生活质量，防止不必要的手术。
Gaucher disease (GD, ORPHA355) is a rare autosomal recessive genetic disease caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). Here, we report a patient with GD who carried the heterozygous c.1240G > C (p.Val414Leu) mutation and the heterozygous pathogenic c.1342G > C (p.Asp448His) mutation in GBA1. Bioinformatics analysis suggested that the two mutations are pathogenic. Functional studies showed that GBA1 mRNA and GCase protein levels of mutant types were significantly less than the wild-type. In the cell lysates, the two mutations of GBA1 c.1240G > C and c.1342G > C caused a decreased GCase concentration, while the two mutations did not change the distribution in the cell. The pathogenicity of the compound heterozygous mutations was verified. Early diagnosis and treatment can improve the quality of life and prevent unnecessary procedures in patients with GD.
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