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Abstract：
BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder caused by mutations in TYMP gene, encoding nuclear thymidine phosphorylase (TP). MNGIE mainly presents with gastrointestinal symptoms and is mostly misdiagnosed in many patients as malabsorption syndrome, inflammatory bowel disease, anorexia nervosa, and intestinal pseudo-obstruction. Up to date, more than 80 pathogenic and likely pathogenic mutations associated with the disease have been reported in patients from a wide range of ethnicities. The objective of this study was to investigate the underlying genetic abnormalities in a 25-year-old woman affected with MNGIE.
METHODS: The patient was a 25-year-old female referred to our center with the chief complaint of severe abdominal pain and diarrhea for 2 years that had worsened from 2 months prior to admission. The clinical and para-clinical findings were in favor of mitochondrial neurogastrointestinal encephalomyopathy syndrome. Subsequent genetic studies revealed a novel, private, homozygous nonsense mutation in TYMP gene (c. 1013 C > A, p.S338X). Sanger sequencing confirmed the new mutation in the proband. Multiple sequence alignment showed high conservation of amino acids of this protein across different species.
CONCLUSIONS: The detected new nonsense mutation in the TYMP gene would be very important for genetic counseling and subsequent early diagnosis and initiation of proper therapy. This novel pathogenic variant would help us establish future genotype-phenotype correlations and identify different pathways related to this disorder.
METHODS: The patient was a 25-year-old female referred to our center with the chief complaint of severe abdominal pain and diarrhea for 2 years that had worsened from 2 months prior to admission. The clinical and para-clinical findings were in favor of mitochondrial neurogastrointestinal encephalomyopathy syndrome. Subsequent genetic studies revealed a novel, private, homozygous nonsense mutation in TYMP gene (c. 1013 C > A, p.S338X). Sanger sequencing confirmed the new mutation in the proband. Multiple sequence alignment showed high conservation of amino acids of this protein across different species.
CONCLUSIONS: The detected new nonsense mutation in the TYMP gene would be very important for genetic counseling and subsequent early diagnosis and initiation of proper therapy. This novel pathogenic variant would help us establish future genotype-phenotype correlations and identify different pathways related to this disorder.
摘要：
背景：线粒体神经胃肠脑肌病（MNGIE）是一种由TYMP基因突变引起的罕见常染色体隐性遗传疾病，编码核胸苷磷酸化酶（TP）。MNGIE主要表现为胃肠道症状，许多患者大多误诊为吸收不良综合征，炎症性肠病，神经性厌食症,和肠道假性梗阻。到目前为止,据报道,在来自不同种族的患者中,有超过80种与该疾病相关的致病性和可能的致病性突变.这项研究的目的是调查患有MNGIE的25岁女性的潜在遗传异常。
方法：患者是一名25岁女性，转诊到我们中心，主诉严重腹痛和腹泻2年，从入院前2个月开始恶化。临床和副临床发现有利于线粒体神经胃肠脑肌病综合征。随后的基因研究揭示了一个新的，私人,TYMP基因的纯合无义突变（c。1013C>A,p.S338X)。Sanger测序证实了先证者中的新突变。多序列比对显示该蛋白质的氨基酸在不同物种中的高度保守性。
结论：在TYMP基因中检测到的新的无义突变对于遗传咨询和随后的早期诊断以及开始适当的治疗非常重要。这种新的致病变异将帮助我们建立未来的基因型-表型相关性，并确定与该疾病相关的不同途径。
方法：患者是一名25岁女性，转诊到我们中心，主诉严重腹痛和腹泻2年，从入院前2个月开始恶化。临床和副临床发现有利于线粒体神经胃肠脑肌病综合征。随后的基因研究揭示了一个新的，私人,TYMP基因的纯合无义突变（c。1013C>A,p.S338X)。Sanger测序证实了先证者中的新突变。多序列比对显示该蛋白质的氨基酸在不同物种中的高度保守性。
结论：在TYMP基因中检测到的新的无义突变对于遗传咨询和随后的早期诊断以及开始适当的治疗非常重要。这种新的致病变异将帮助我们建立未来的基因型-表型相关性，并确定与该疾病相关的不同途径。
