Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
Eur J Hum Genet. 2018 Jun;26(6):808-817. doi: 10.1038/s41431-018-0122-6. Epub 2018 Feb 26.
γ-Glutamyl transpeptidase deficiency (glutathionuria, OMIM 231950) is a rare disease, with only six patients reported in the literature, although this condition has probably been underdiagnosed due the difficulty to routinely analyze glutathione in clinical samples and to the fact that no genetic defect has been coupled to the disease so far. We report two siblings with mild psychomotor developmental delay and mild neurological symptoms, who presented a markedly increased excretion of glutathione in urine and a very low γ-glutamyl transpeptidase activity in serum. Whole-genome sequencing revealed the presence of a 16.9 kb homozygous deletion in GGT1, one of the genes encoding enzymes with γ-glutamyl transpeptidase activity in the human genome. Close analysis revealed the presence of a 13 bp insertion at the deletion junction. This is the first report of a genetic variant as the cause of glutathionuria. In addition, genetic characterization of the patients' parents and a healthy sibling has provided direct genetic evidence regarding the autosomal recessive nature of this disease.
γ-谷氨酰转肽酶缺乏症（谷胱甘肽尿症，OMIM 231950）是一种罕见疾病，文献中仅报道了六例患者，尽管由于难以在临床样本中常规分析谷胱甘肽，以及迄今为止尚未发现与该疾病相关的遗传缺陷，这种疾病可能被误诊。我们报告了两例有轻度精神运动发育迟缓及轻度神经症状的同胞，他们的尿液中谷胱甘肽排泄明显增加，血清中γ-谷氨酰转肽酶活性非常低。全基因组测序显示 GGT1 基因中存在 16.9kb 的纯合缺失，GGT1 是人类基因组中具有 γ-谷氨酰转肽酶活性的酶的基因之一。仔细分析发现缺失连接处存在 13bp 的插入。这是首次报道遗传变异是谷胱甘肽尿症的病因。此外，对患者父母和健康同胞的遗传特征分析提供了关于该疾病常染色体隐性遗传性质的直接遗传证据。
