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.
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。