不明原因新生儿高胆红素血症331例遗传因素分析

Genetic analysis in 331 cases of neonatal hyperbilirubinemia with unknown etiology

目的探讨广东地区不明原因新生儿高胆红素血症遗传因素及进行新生儿黄疸相关基因筛查的临床意义。方法选择2021年7~9月广东地区出生的不明原因高胆红素血症新生儿进行前瞻性研究, 采用基于目的基因捕获的高通量测序技术对24个新生儿黄疸相关基因的外显子区域进行检测, 对变异致病性进行解读并对检测结果进行统计分析。结果在331例高胆红素血症新生儿中, 筛出阳性患儿139例(42.0%), 包含5种疾病, Gilbert综合征65例(19.6%), 葡萄糖-6-磷酸脱氢酶缺乏症48例(14.5%), 钠牛磺胆酸共转运多肽缺陷病18例(5.4%), Citrin缺乏症4例(1.2%), Dubin-Johnson综合征4例(1.2%)。149例(45.0%)携带1个或多个基因变异位点, 43例(13.0%)未检出有临床意义的变异位点。8个高频变异位点(携带率>1%)为UGT1A1基因c.211G>A和c.1091C>T位点、G6PD基因c.1466G>T和c.1478G>A位点、SLC10A1基因c.800C>T位点、SLC25A13基因c.852_55del TATG位点、HBB基因c.12629delCTTT和c.316-197C>T位点。结论遗传因素是广东地区不明原因新生儿高胆红素血症发病的重要因素, 常见致病基因是UGT1A1基因、G6PD基因、SLC10A1基因和SLC25A13基因, 且存在人群高频携带位点, 对不明原因高胆红素血症患儿进行基因检测具有重要临床意义。

Objective To study the genetic profile of neonatal hyperbilirubinemia with unknown etiology in Guangdong Province and the clinical significance of jaundice-related genetic screening.Methods From July to September,2021,neonates with hyperbilirubinemia of unknown etiology born in different hospitals in Guangdong Province were studied.24 neonatal jaundice-related exons were sequenced using targeted capture and high-throughput sequencing technology.The pathogenic variants were analyzed.Results A total of 331 cases,139(42.0%)cases showed positive screening results with five diseases,including 65(19.6%)cases of Gilbert syndrome,48(14.5%)cases of glucose-6-phosphate dehydrogenase(G6PD)deficiency,18(5.4%)cases of sodium taurocholate cotransporting polypeptide deficiency,4(1.2%)cases of Citrin deficiency and 4(1.2%)cases of Dubin-Johnson syndrome.149(45.0%)cases carried one or more genetic variants and 43(13.0%)cases showed no clinically significant variants.The 8 high-frequency mutation loci(carrier rate>1%)are UGT1A1 gene c.211G>A and c.1091C>T,G6PD gene c.1466G>T and c.1478G>A,SLC10A1 gene c.800C>T,SLC25A13 gene c.852_855del TATG,HBB gene c.126_129delCTTT and c.316-197C>T.Conclusions Genetic factors are important for neonatal hyperbilirubinemia with unknown etiology in Guangdong.The common pathogenic genes are UGT1A1,G6PD,SLC10A1,and SLC25A13 and the population carries high-frequency mutation loci.Therefore,genetic screening in neonates with hyperbilirubinemia of unknown etiology has important clinical significance.