Characterization of a novel TYMP

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• 作者：Jan-Willem Taanman ; Mariza Daras ; Juliane Albrecht ; Charles A. Davie ; Elizabeth A. Mallam ; John R. Muddle ; Mark Weatherall ; Thomas T. Warner ; Anthony H.V. Schapira ; Lionel Ginsberg
• 关键词：Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) ; Thymidine phosphorylase ; TYMP ; Mitochondrial DNA
• 刊名：Neuromuscular Disorders
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：19
• 期：2
• 页码：151-154
• 全文大小：923 K

文摘

Mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive disorder caused by loss-of-function mutations in the thymidine phosphorylase gene (TYMP). We report here a patient compound heterozygous for two TYMP mutations: a novel g.4009G>A transition affecting the consensus splice donor site of intron 9, and a previously reported g.675G>C splice site mutation. The novel mutation causes exon 9 skipping but leaves the reading frame intact; however, TYMP protein was not detected by immunoblot analysis, suggesting that neither mutant allele is expressed as protein. The patient’s fibroblasts showed gradual loss of the mitochondrial DNA-encoded subunit I of cytochrome-c oxidase, suggesting a progressive mitochondrial DNA defect in culture.