Biallelic mutations in GPD1 gene in a Chinese boy mainly presented with obesity, insulin resistance, fatty liver, and short stature
Biallelic mutations in GPD1 gene in a Chinese boy mainly presented with obesity, insulin resistance, fatty liver, and short stature
复制标题
中国男孩GPD1基因双等位基因突变，主要表现为肥胖、胰岛素抵抗、脂肪肝、身材矮小
DOI：
10.1002/ajmg.a.38473
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发表时间：
2017-12-01
影响因子：
2
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Li, Niu;Chang, Guoying;Wang, Jian
GPD 1基因中的双等位基因突变导致一种罕见的常染色体隐性遗传疾病，称为短暂性婴儿高胆固醇血症（OMIM #614480）。到目前为止，只有五个致病性变异已报告在15例患者从三项研究。受影响个体的临床症状呈现一定程度的异质性。在这里，我们描述了一个中国青少年患者谁主要表现为肥胖，胰岛素抵抗，脂肪肝，身材矮小。靶向下一代测序揭示了GPD 1基因中的一种新型复合杂合变体（c.220 - 2A>G和c.820G>A; p.Ala274Thr）。体外研究表明，Ala 274 Thr变体诱导GPD 1蛋白表达的降低。对HEK 293细胞中小基因构建体中剪接模式的进一步体外研究表明，c.220 - 2A>G变体产生了外显子3中具有一个隐蔽剪接位点的改变的转录物，导致外显子3中69个碱基的丢失（c.220_288del，p.74_96del）。这是第一份涉及亚洲人携带GPD 1突变的报告。我们的工作不仅扩大了GPD 1基因的突变谱，而且还提供了关于其表型的新见解。
Biallelic mutations in the GPD1 gene cause a rare autosomal recessive inherited disease known as transient infantile hypertriglyceridemia (OMIM #614480). To date, only five pathogenic variants have been reported in 15 patients from three studies. The clinical symptoms of the affected individuals present a certain degree of heterogeneity. Here, we describe a chinese adolescent patient who mainly presented with obesity, insulin resistance, fatty liver, and short stature. Targeted next‐generation sequencing revealed a novel compound heterozygous variant in GPD1 gene (c.220‐2A>G and c.820G>A; p.Ala274Thr). In vitro studies demonstrated that the Ala274Thr variant induced a decrease in GPD1 protein expression. Further in vitro investigation of the splicing pattern in a minigene construct in HEK293 cells showed that the c.220‐2A>G variant generated an altered transcript with one cryptic splice site in exon 3, resulting in the loss of 69 bases in exon 3 (c.220_288del, p.74_96del). This is the first report involving an Asian who harbored GPD1 mutations. Our work not only expands the mutant spectrum of the GPD1 gene but also provides new insights on its resulting phenotype.