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Abstract：
BACKGROUND: Neonatal hyperbilirubinemia is a common problem faced by pediatricians. The role of genetic factors in neonatal jaundice has been gradually recognized. This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing (NGS).
METHODS: Five neonates with severe hyperbilirubinemia were retrospectively studied. They exhibited bilirubin encephalopathy, hypothyroidism, ABO blood type incompatibility hemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency and premature birth, respectively. A customized 22-gene panel was designed, and NGS was carried out for these neonates. Eight variations (G6PD c.G1388A, HBA2 c.C369G, ABCC2 c.C3825G, UGT1A1 c.G211A, SPTB c.A1729G, EPB41 c.G520A, c.1213-4T>G and c.A1474G) were identified in these five neonates. Genetic mutations of these genes are associated with G6PD deficiency, thalassemia, Dubin-Johnson syndrome, Gilbert syndrome, hereditary spherocytosis, and hereditary elliptocytosis. One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A (p.E174K), but no elliptocyte was seen on his blood smear of 4 years old.
CONCLUSIONS: Pathological factors of severe neonatal hyperbilirubinemia are complicated. Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia, and severe jaundice in neonates may be related to a cumulative effect of genetic variants.
METHODS: Five neonates with severe hyperbilirubinemia were retrospectively studied. They exhibited bilirubin encephalopathy, hypothyroidism, ABO blood type incompatibility hemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency and premature birth, respectively. A customized 22-gene panel was designed, and NGS was carried out for these neonates. Eight variations (G6PD c.G1388A, HBA2 c.C369G, ABCC2 c.C3825G, UGT1A1 c.G211A, SPTB c.A1729G, EPB41 c.G520A, c.1213-4T>G and c.A1474G) were identified in these five neonates. Genetic mutations of these genes are associated with G6PD deficiency, thalassemia, Dubin-Johnson syndrome, Gilbert syndrome, hereditary spherocytosis, and hereditary elliptocytosis. One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A (p.E174K), but no elliptocyte was seen on his blood smear of 4 years old.
CONCLUSIONS: Pathological factors of severe neonatal hyperbilirubinemia are complicated. Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia, and severe jaundice in neonates may be related to a cumulative effect of genetic variants.
摘要：
背景：新生儿高胆红素血症是儿科医生面临的常见问题。遗传因素在新生儿黄疸中的作用已逐渐得到认可。这项研究旨在使用下一代测序（NGS）确定影响五名患者胆红素水平的遗传变异。
方法：对5例重度高胆红素血症新生儿进行回顾性分析。他们表现出胆红素脑病，甲状腺功能减退,ABO血型不相容溶血，葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症和早产，分别。设计了一个定制的22基因面板，并对这些新生儿进行了NGS。八个变体(G6PDc.G1388A,HBA2c.C369G,ABCC2c.C3825G,UGT1A1c.G211A,SPTBc.A1729G,EPB41c.G520A,在这五名新生儿中鉴定出c.1213-4T>G和c.A1474G)。这些基因的基因突变与G6PD缺乏有关,地中海贫血,杜宾-约翰逊综合征,吉尔伯特综合征,遗传性球形红细胞增多症,和遗传性椭圆形细胞。发现其中一名新生儿具有EPB41剪接位点c.1213-4T>G和c.G520A的复合变体（p。E174K),但是在他4岁的血涂片上没有看到椭圆细胞。
结论：重度新生儿高胆红素血症的病理因素复杂。遗传变异可能在新生儿高胆红素血症的风险增加中起重要作用。新生儿的严重黄疸可能与遗传变异的累积效应有关。
方法：对5例重度高胆红素血症新生儿进行回顾性分析。他们表现出胆红素脑病，甲状腺功能减退,ABO血型不相容溶血，葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症和早产，分别。设计了一个定制的22基因面板，并对这些新生儿进行了NGS。八个变体(G6PDc.G1388A,HBA2c.C369G,ABCC2c.C3825G,UGT1A1c.G211A,SPTBc.A1729G,EPB41c.G520A,在这五名新生儿中鉴定出c.1213-4T>G和c.A1474G)。这些基因的基因突变与G6PD缺乏有关,地中海贫血,杜宾-约翰逊综合征,吉尔伯特综合征,遗传性球形红细胞增多症,和遗传性椭圆形细胞。发现其中一名新生儿具有EPB41剪接位点c.1213-4T>G和c.G520A的复合变体（p。E174K),但是在他4岁的血涂片上没有看到椭圆细胞。
结论：重度新生儿高胆红素血症的病理因素复杂。遗传变异可能在新生儿高胆红素血症的风险增加中起重要作用。新生儿的严重黄疸可能与遗传变异的累积效应有关。
