基因panel在新生儿疑似遗传代谢疾病中的应用

Application of Gene Panel in Neonates with Suspected Inherited Metabolic Diseases

目的探讨基因panel在患有疑似遗传代谢疾病新生儿中的应用。方法对华中科技大学同济医学院附属同济医院2023年1月—2024年3月收治的有遗传代谢高危临床表型的新生儿,采用基因panel检测,同时搜集其临床资料并进行随访观察,分析致病基因的检出情况、患儿基因型与表型的一致性等。结果该研究共纳入53例有遗传代谢高危征象的新生儿,其中致病基因阳性的总体检出率为17.0%(9/53),常见检出的致病基因有氯离子通道基因(CLCN1)、双氧化酶2基因(DUOX2)、间隙连接蛋白β2基因(GJB2)、酪氨酸蛋白磷酸酶非受体11型基因(PTPN11)、钠通道α亚基基因(SCN1A)、痉挛截瘫基因11(SPG11)等,其中DUOX2和GJB2检出比例最高,分别为33.3%(3/9)和22.2%(2/9)。将致病基因阳性组患儿与阴性组患儿进行对比分析,阳性组患儿临床表型个数可能更多,预后相较于基因阴性组也更严重。在致病基因阳性组患儿中,除了病例1和病例9因相关疾病发病较晚导致临床表型与致病基因暂时不相符,其余病例致病基因与临床表型均符合。结论基因panel具有耗时短、检测成本及技术难度低等特点,适用于发展中国家及经济水平相对落后地区疑似遗传代谢疾病患儿的早期筛查。

Objective To investigate the application of gene panel in neonates with suspected genetic metabolic diseases.Methods The gene panel designed by Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology was used to screen newborns exhibiting high-risk clinical phenotypes of genetic metabolic diseases from January 2023 to March 2024.Meanwhile,the clinical data were collected and follow-up observations were conducted to analyze the detection rates of pathogenic genes and the correlation between genotype and phenotype of the neonates.Results A total of 53 neonates with high-risk inherited metabolic clinical phenotypes were included in this study,among which the overall positive detection rate for pathogenic genes was 17.0%(9/53).The pathogenic genes detected in this study were chloride channel(CLCN1),dual oxidase 2(DUOX2),gap junction protein beta 2(GJB2),tyrosine-protein phosphatase nonreceptor type 11(PTPN11),sodium channelαsubunit(SCN1A),spastic paraplegia gene 11(SPG11),etc.DUOX2 and GJB2 were the most frequently detected,accounting for 33.3%(3/9)and 22.2%(2/9)of positive cases,respectively.A comparative analysis was made between the positive and negative groups of pathogenic genes,and it was found that the prognosis of the positive group was more serious and the number of clinical phenotypes might be more than that of the negative group.In the positive group of pathogenic genes,except for cases 1 and 9,whose clinical phenotypes were temporarily inconsistent with pathogenic genes due to the late onset of related diseases,the pathogenic genes were consistent with clinical phenotypes in the remaining cases.Conclusion The gene panel,characterized by short detection time,low detection cost and minimal technical demands,are suitable for the early screening of neonates with suspected genetic metabolic diseases in developing countries and economically backward areas.