Abstract：
OBJECTIVE: To assess the value of genetic screening by high-throughput sequencing (HTS) for the early diagnosis of neonatal diseases.
METHODS: A total of 2 060 neonates born at Ningbo Women and Children\'s Hospital from March to September 2021 were selected as the study subjects. All neonates had undergone conventional tandem mass spectrometry metabolite analysis and fluorescent immunoassay analysis. HTS was carried out to detect the definite pathogenic variant sites with high-frequency of 135 disease-related genes. Candidate variants were verified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA).
RESULTS: Among the 2 060 newborns, 31 were diagnosed with genetic diseases, 557 were found to be carriers, and 1 472 were negative. Among the 31 neonates, 5 had G6PD, 19 had hereditary non-syndromic deafness due to variants of GJB2, GJB3 and MT-RNR1 genes, 2 had PAH gene variants, 1 had GAA gene variants, 1 had SMN1 gene variants, 2 had MTTL1 gene variants, and 1 had GH1 gene variants. Clinically, 1 child had Spinal muscular atrophy (SMA), 1 had Glycogen storage disease II, 2 had congenital deafness, and 5 had G6PD deficiency. One mother was diagnosed with SMA. No patient was detected by conventional tandem mass spectrometry. Conventional fluorescence immunoassay had revealed 5 cases of G6PD deficiency (all positive by genetic screening) and 2 cases of hypothyroidism (identified as carriers). The most common variants identified in this region have involved DUOX2 (3.93%), ATP7B (2.48%), SLC26A4 (2.38%), GJB2 (2.33%), PAH (2.09%) and SLC22A5 genes (2.09%).
CONCLUSIONS: Neonatal genetic screening has a wide range of detection and high detection rate, which can significantly improve the efficacy of newborn screening when combined with conventional screening and facilitate secondary prevention for the affected children, diagnosis of family members and genetic counseling for the carriers.
METHODS: A total of 2 060 neonates born at Ningbo Women and Children\'s Hospital from March to September 2021 were selected as the study subjects. All neonates had undergone conventional tandem mass spectrometry metabolite analysis and fluorescent immunoassay analysis. HTS was carried out to detect the definite pathogenic variant sites with high-frequency of 135 disease-related genes. Candidate variants were verified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA).
RESULTS: Among the 2 060 newborns, 31 were diagnosed with genetic diseases, 557 were found to be carriers, and 1 472 were negative. Among the 31 neonates, 5 had G6PD, 19 had hereditary non-syndromic deafness due to variants of GJB2, GJB3 and MT-RNR1 genes, 2 had PAH gene variants, 1 had GAA gene variants, 1 had SMN1 gene variants, 2 had MTTL1 gene variants, and 1 had GH1 gene variants. Clinically, 1 child had Spinal muscular atrophy (SMA), 1 had Glycogen storage disease II, 2 had congenital deafness, and 5 had G6PD deficiency. One mother was diagnosed with SMA. No patient was detected by conventional tandem mass spectrometry. Conventional fluorescence immunoassay had revealed 5 cases of G6PD deficiency (all positive by genetic screening) and 2 cases of hypothyroidism (identified as carriers). The most common variants identified in this region have involved DUOX2 (3.93%), ATP7B (2.48%), SLC26A4 (2.38%), GJB2 (2.33%), PAH (2.09%) and SLC22A5 genes (2.09%).
CONCLUSIONS: Neonatal genetic screening has a wide range of detection and high detection rate, which can significantly improve the efficacy of newborn screening when combined with conventional screening and facilitate secondary prevention for the affected children, diagnosis of family members and genetic counseling for the carriers.
摘要：
目的：探讨高通量测序基因筛查在新生儿疾病早期诊断中的价值。
方法：选取2021年3-9月在宁波市妇女儿童医院出生的2060例新生儿作为研究对象。所有新生儿均进行了常规串联质谱代谢产物分析和荧光免疫分析。进行HTS以检测具有135个疾病相关基因的高频率的明确致病变异位点。通过Sanger测序或多重连接依赖性探针扩增(MLPA)验证候选变体。
结果：在2060名新生儿中，31人被诊断患有遗传疾病，557人被发现是携带者，1472例为阴性。在31名新生儿中，5有G6PD,由于GJB2，GJB3和MT-RNR1基因的变异，19名患有遗传性非综合征性耳聋，2有PAH基因变异，1有GAA基因变异，1有SMN1基因变异，2有MTTL1基因变异，1有GH1基因变异。临床上,1名儿童患有脊髓性肌萎缩症（SMA），1患有糖原贮积病II，2有先天性耳聋，5人患有G6PD缺乏症。一位母亲被诊断出患有SMA。通过常规串联质谱法未检测到患者。常规荧光免疫分析显示5例G6PD缺乏症（遗传筛查均为阳性）和2例甲状腺功能减退（确定为携带者）。该区域最常见的变异涉及DUOX2（3.93%），ATP7B（2.48%），SLC26A4（2.38%），GJB2（2.33%），PAH(2.09%)和SLC22A5基因(2.09%)。
结论：新生儿基因筛查检测范围广、检出率高，与常规筛查相结合，可以显着提高新生儿筛查的效果，并促进受影响儿童的二级预防，家庭成员的诊断和携带者的遗传咨询。
方法：选取2021年3-9月在宁波市妇女儿童医院出生的2060例新生儿作为研究对象。所有新生儿均进行了常规串联质谱代谢产物分析和荧光免疫分析。进行HTS以检测具有135个疾病相关基因的高频率的明确致病变异位点。通过Sanger测序或多重连接依赖性探针扩增(MLPA)验证候选变体。
结果：在2060名新生儿中，31人被诊断患有遗传疾病，557人被发现是携带者，1472例为阴性。在31名新生儿中，5有G6PD,由于GJB2，GJB3和MT-RNR1基因的变异，19名患有遗传性非综合征性耳聋，2有PAH基因变异，1有GAA基因变异，1有SMN1基因变异，2有MTTL1基因变异，1有GH1基因变异。临床上,1名儿童患有脊髓性肌萎缩症（SMA），1患有糖原贮积病II，2有先天性耳聋，5人患有G6PD缺乏症。一位母亲被诊断出患有SMA。通过常规串联质谱法未检测到患者。常规荧光免疫分析显示5例G6PD缺乏症（遗传筛查均为阳性）和2例甲状腺功能减退（确定为携带者）。该区域最常见的变异涉及DUOX2（3.93%），ATP7B（2.48%），SLC26A4（2.38%），GJB2（2.33%），PAH(2.09%)和SLC22A5基因(2.09%)。
结论：新生儿基因筛查检测范围广、检出率高，与常规筛查相结合，可以显着提高新生儿筛查的效果，并促进受影响儿童的二级预防，家庭成员的诊断和携带者的遗传咨询。
