Glucose-6-phosphate dehydrogenase deficiency (D-G6PD) is an X-linked recessive disorder resulted from deleterious variants in the housekeeping gene Glucose-6-phosphate 1-dehydrogenase (G6PD), causing impaired response to oxidizing agents. Screening for new variations of the gene helps with early diagnosis of D-G6PD resulting in a reduction of disease related complications and ultimately increased life expectancy of the patients. One thousand five hundred sixty-five infants with pathological jaundice were screened for G6PD variants by Sanger sequencing all of the 13 exons, and the junctions of exons and introns of the G6PD gene. We detected G6PD variants in 439 (28.1%) of the 1565 infants with pathological jaundice. In total, 9 types of G6PD variants were identified in our cohort; and a novel G6PD missense variant c.1118 T > C, p.Phe373Ser in exon 9 of the G6PD gene was detected in three families. Infants with this novel variant showed decreased activity of G6PD, severe anemia, and pathological jaundice, consistent with Class I G6PD deleterious variants. Analysis of the resulting protein’s structure revealed this novel variant affects G6PD protein stability, which could be responsible for the pathogenesis of D-G6PD in these patients. High rates of G6PD variants were detected in infants with pathological jaundice, and a novel Class I G6PD deleterious variants was identified in our cohort. Our data reveal that variant analysis is helpful for the diagnosis of D-G6PD in patients, and also for the expansion of the spectrum of known G6PD variants used for carrier detection and prenatal diagnosis.

中文翻译：

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在三个严重的葡萄糖-6-磷酸脱氢酶缺乏症家庭中鉴定出一种新型的G6PD有害变体。

6-磷酸葡萄糖脱氢酶缺乏症（D-G6PD）是一种X连锁隐性疾病，是由管家基因6磷酸葡萄糖1-脱氢酶（G6PD）中的有害变体导致的，导致对氧化剂的反应减弱。筛选基因的新变异有助于早期诊断D-G6PD，从而减少与疾病相关的并发症，并最终提高患者的预期寿命。通过对所有13个外显子以及G6PD基因的外显子和内含子的连接进行Sanger测序，对155例患有病理性黄疸的婴儿进行了G6PD变异体筛选。我们在1565例病理性黄疸婴儿中检测到439例（28.1％）G6PD变异。在我们的队列研究中，总共鉴定出9种类型的G6PD变体。以及新型G6PD错义变体c.1118 T> C，p。在三个家族中检测到G6PD基因第9外显子中的Phe373Ser。具有这种新变异的婴儿表现出G6PD活性降低，严重贫血和病理性黄疸，与I类G6PD有害变异一致。对所得蛋白质结构的分析表明，该新变异影响了G6PD蛋白质的稳定性，这可能是这些患者D-G6PD发病的原因。在患有病理性黄疸的婴儿中检测到高水平的G6PD变异体，并且在我们的队列中发现了一种新的I类G6PD有害变异体。我们的数据表明，变异分析有助于诊断患者的D-G6PD，也有助于扩大用于载体检测和产前诊断的已知G6PD变异的范围。具有这种新变异的婴儿表现出G6PD活性降低，严重贫血和病理性黄疸，与I类G6PD有害变异一致。对所得蛋白质结构的分析表明，该新变异影响了G6PD蛋白质的稳定性，这可能是这些患者D-G6PD发病的原因。在患有病理性黄疸的婴儿中检测到高水平的G6PD变异体，并且在我们的队列中发现了一种新的I类G6PD有害变异体。我们的数据表明，变异分析有助于诊断患者的D-G6PD，也有助于扩大用于载体检测和产前诊断的已知G6PD变异的范围。具有这种新变异的婴儿表现出G6PD活性降低，严重贫血和病理性黄疸，与I类G6PD有害变异一致。对所得蛋白质结构的分析表明，该新变异影响了G6PD蛋白质的稳定性，这可能是这些患者D-G6PD发病的原因。在患有病理性黄疸的婴儿中检测到高水平的G6PD变异体，并且在我们的队列研究中鉴定出了新的I类G6PD有害变异体。我们的数据表明，变异分析有助于诊断患者的D-G6PD，也有助于扩大用于载体检测和产前诊断的已知G6PD变异的范围。对所得蛋白质结构的分析表明，该新变异影响了G6PD蛋白质的稳定性，这可能是这些患者D-G6PD发病的原因。在患有病理性黄疸的婴儿中检测到高水平的G6PD变异体，并且在我们的队列中发现了一种新的I类G6PD有害变异体。我们的数据表明，变异分析有助于诊断患者的D-G6PD，也有助于扩大用于载体检测和产前诊断的已知G6PD变异的范围。对所得蛋白质结构的分析表明，该新变异影响了G6PD蛋白质的稳定性，这可能是这些患者D-G6PD发病的原因。在患有病理性黄疸的婴儿中检测到高水平的G6PD变异体，并且在我们的队列中发现了一种新的I类G6PD有害变异体。我们的数据表明，变异分析有助于患者D-G6PD的诊断，也有助于扩大用于载体检测和产前诊断的已知G6PD变异的范围。在我们的队列研究中发现了一种新的I类G6PD有害变体。我们的数据表明，变异分析有助于诊断患者的D-G6PD，也有助于扩大用于载体检测和产前诊断的已知G6PD变异的范围。在我们的队列研究中发现了一种新的I类G6PD有害变体。我们的数据表明，变异分析有助于诊断患者的D-G6PD，也有助于扩大用于载体检测和产前诊断的已知G6PD变异的范围。