Hypertryptophanemia due to tryptophan 2,3-dioxygenase deficiency.

• 影响指数: 4.204
• 发表时间: 04 2017
• 来源期刊: Mol Genet Metab
• DOI: 10.1016/j.ymgme.2017.02.009
• PMID: 28285122
• 文章类型: Case Reports
• 中科院分区: Q2
• 方向: 医学
• 作者列表: Ferreira P,Shin I,Sosova I,Dornevil K,Jain S,Dewey D,Liu F,Liu A

关键词: Hyperserotoninemia; Hypertryptophanemia; TDO2; Tryptophan 2,3-dioxygenase

Mesh: Amino Acid Metabolism, Inborn Errors / genetics; Catalytic Domain; Female; Genetic Predisposition to Disease; HeLa Cells; Humans; Infant, Newborn; Mutation; Protein Structure, Tertiary; Sequence Analysis, DNA; Tryptophan Oxygenase / chemistry genetics

Abstract

In this report we describe the first human case of hypertryptophanemia confirmed to be due to tryptophan 2,3-dioxygenase deficiency. The underlying etiology was established by sequencing the TDO2 gene, in which there was compound heterozygosity for two rare variants: c.324G>C, p.Met108Ile and c.491dup, p.Ile165Aspfs*12. The pathogenicity of these variants was confirmed by molecular-level studies, which showed that c.491dup does not produce soluble protein and c.324G>C results in a catalytically less efficient Met108Ile enzyme that is prone to proteolytic degradation. The biochemical phenotype of hypertryptophanemia and hyperserotoninemia does not appear to have significant clinical consequences.