Abstract：
OBJECTIVE: To analyze the types and distribution of pathogenic variants for neonatal genetic diseases in Huzhou, Zhejiang Province.
METHODS: One thousand neonates (48 ~ 42 h after birth) born to Huzhou region were selected as the study subjects. Dry blood spot samples were collected from the newborns, and targeted capture high-throughput sequencing was carried out for pathogenic genes underlying 542 inherited diseases. Candidate variants were verified by Sanger sequencing.
RESULTS: Among the 1 000 newborns, the male to female ratio was 1.02 : 1.00. No pathogenic variants were detected in 253 cases, whilst 747 cases were found to carry at least one pathogenic variant, which yielded a carrier rate of 74.7%. The most frequently involved pathogenic gene was FLG, followed by GJB2, UGT1A1, USH2A and DUOX2. The variants were classified as homozygous, compound heterozygous, and hemizygous variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), 213 neonates were verified to have carried pathogenic and/or likely pathogenic variants, with a positive rate of 21.3%. The most commonly involved genes had included UGT1A1, FLG, GJB2, MEFV and G6PD.
CONCLUSIONS: Newborn screening based on high-throughput sequencing technology can expand the scope of screening and improve the positive predictive value. Genetic counseling based on the results can improve the patients\' medical care and reduce neonatal mortality and childhood morbidity, while provide assistance to family members\' health management and reproductive decisions.
METHODS: One thousand neonates (48 ~ 42 h after birth) born to Huzhou region were selected as the study subjects. Dry blood spot samples were collected from the newborns, and targeted capture high-throughput sequencing was carried out for pathogenic genes underlying 542 inherited diseases. Candidate variants were verified by Sanger sequencing.
RESULTS: Among the 1 000 newborns, the male to female ratio was 1.02 : 1.00. No pathogenic variants were detected in 253 cases, whilst 747 cases were found to carry at least one pathogenic variant, which yielded a carrier rate of 74.7%. The most frequently involved pathogenic gene was FLG, followed by GJB2, UGT1A1, USH2A and DUOX2. The variants were classified as homozygous, compound heterozygous, and hemizygous variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), 213 neonates were verified to have carried pathogenic and/or likely pathogenic variants, with a positive rate of 21.3%. The most commonly involved genes had included UGT1A1, FLG, GJB2, MEFV and G6PD.
CONCLUSIONS: Newborn screening based on high-throughput sequencing technology can expand the scope of screening and improve the positive predictive value. Genetic counseling based on the results can improve the patients\' medical care and reduce neonatal mortality and childhood morbidity, while provide assistance to family members\' health management and reproductive decisions.
摘要：
目的:分析湖州市新生儿遗传病的致病变异类型及分布,浙江省。
方法：选择湖州地区出生的新生儿（出生后48〜42h）为研究对象。从新生儿身上采集干血斑样本,并对542种遗传性疾病的致病基因进行了靶向捕获高通量测序。通过Sanger测序验证候选变体。
结果：在1000名新生儿中，男女比例为1.02:1.00。253例未检出致病变异,同时发现747例病例携带至少一种致病变体，这产生了74.7%的载波率。最常见的致病基因是FLG，其次是GJB2、UGT1A1、USH2A和DUOX2。变体被分类为纯合的，复合杂合，和半合子变体。根据美国医学遗传学和基因组学学院（ACMG）的指南，213名新生儿被证实携带致病性和/或可能的致病性变异，阳性率为21.3%。最常见的基因包括UGT1A1，FLG，GJB2、MEFV和G6PD。
结论：基于高通量测序技术的新生儿筛查可扩大筛查范围，提高阳性预测值。基于结果的遗传咨询可以改善患者的医疗护理，降低新生儿死亡率和儿童发病率，同时为家庭成员的健康管理和生殖决策提供帮助。
方法：选择湖州地区出生的新生儿（出生后48〜42h）为研究对象。从新生儿身上采集干血斑样本,并对542种遗传性疾病的致病基因进行了靶向捕获高通量测序。通过Sanger测序验证候选变体。
结果：在1000名新生儿中，男女比例为1.02:1.00。253例未检出致病变异,同时发现747例病例携带至少一种致病变体，这产生了74.7%的载波率。最常见的致病基因是FLG，其次是GJB2、UGT1A1、USH2A和DUOX2。变体被分类为纯合的，复合杂合，和半合子变体。根据美国医学遗传学和基因组学学院（ACMG）的指南，213名新生儿被证实携带致病性和/或可能的致病性变异，阳性率为21.3%。最常见的基因包括UGT1A1，FLG，GJB2、MEFV和G6PD。
结论：基于高通量测序技术的新生儿筛查可扩大筛查范围，提高阳性预测值。基于结果的遗传咨询可以改善患者的医疗护理，降低新生儿死亡率和儿童发病率，同时为家庭成员的健康管理和生殖决策提供帮助。
