Novel Association of Early Onset Hepatocellular Carcinoma with Transaldolase Deficiency
Novel Association of Early Onset Hepatocellular Carcinoma with Transaldolase Deficiency
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DOI：
10.1007/8904_2013_254
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发表时间：
2014-01-01
期刊：
影响因子：
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通讯作者：
Chung, Wendy K.
中科院分区：
文献类型：
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作者：
LeDuc, Charles A.;Crouch, Elizabeth E.;Chung, Wendy K.
我们评估了一个家庭，一个16个月大的男孩患有肝硬化和肝细胞癌，他30个月大的弟弟患有肝硬化。在常规代谢评估后未能确定诊断后，我们利用RNA-Seq和全外显子组测序的组合来确定先证者，他的肝硬化兄弟以及临床上无症状的8岁哥哥中的新型纯合p.Ser171Phe转醛醇酶（TALDO 1）变体。TALDO 1的代谢物分析和酶检测表明核糖醇、景天庚糖醇和景天庚酮糖-7 β升高，并且在p.Ser171Phe突变纯合子的三个儿童中缺乏TALDO 1的活性。我们的研究结果扩大了转醛醇酶缺乏症的表型，包括人类早发性肝细胞癌，并表明，即使在同一个家庭，具有相同的纯合突变的个体表现出广泛的表型。
We evaluated a family with a 16-month-old boy with cirrhosis and hepatocellular carcinoma and his 30-month-old brother with cirrhosis. After failing to identify a diagnosis after routine metabolic evaluation, we utilized a combination of RNA-Seq and whole exome sequencing to identify a novel homozygous p.Ser171Phe Transaldolase (TALDO1) variant in the proband, his brother with cirrhosis, as well as a clinically asymptomatic older 8-year-old brother. Metabolite analysis and enzymatic testing of TALDO1 demonstrated elevated ribitol, sedoheptitol, and sedoheptulose-7P, and lack of activity of TALDO1 in the three children homozygous for the p.Ser171Phe mutation. Our findings expand the phenotype of transaldolase deficiency to include early onset hepatocellular carcinoma in humans and demonstrate that, even within the same family, individuals with the same homozygous mutation demonstrate a wide range of phenotypes.