Abstract: Objective To explore the significance of whole genome sequencing(WGS) technology in the screening of genetic diseases in infants under 3 months old, in order to provide a new direction for precise diagnosis of genetic diseases. Methods Infants with clinically undiagnosed suspected genetic diseases who underwent WGS analysis in the neonatal ward of Baoding Hospital of Beijing Children′s Hospital Affiliated to Capital Medical University from April 2019 to April 2024, were selected as study subjects. Clinical data were collected to assess the significance of WGS technology in genetic diseases. Results A total of 82 infants were included, and genetic abnormalities were detected in 38 cases, with a detection rate of 46.34%(38/82). Among them, there were 3 cases of Gilbert syndrome, 2 cases of epidermolysis bullosa, 2 cases of Coffin-Siris syndrome, 2 cases of Prader Willi/Angelman syndrome, 2 cases of methylmalonic acidemia mut(0) type, 2 cases of methylmalonic acidemia with homocystinuria CblC type, and 1 case each of Sjogren-Larsson syndrome, maple syrup urine disease type 2, central gigantism syndrome type 2, Neurofibromatosis-Noonan syndrome/neurofibromatosis type 1, Marshall syndrome, X-linked congenital adrenal hypoplasia, Treacher Collins syndrome type 1, multiple congenital anomalies-hypotonia-seizure syndrome, autosomal dominant cutis laxa type 1, congenital central hypoventilation syndrome, spinal muscular atrophy type 2, 16p11.2 deletion syndrome with a 220kb deletion, dilated cardiomyopathy 1CC type, 11q23.3q25 copy number duplication, Kabuki syndrome type 2, Menkes disease, mitochondrial DNA mutation, xeroderma pigmentosum, immunodeficiency type 104, hypohidrotic ectodermal dysplasia, idiopathic infantile arterial calcification, neonatal severe encephalopathy, G6PD-deficient hemolytic anemia, CHARGE syndrome, and Niemann-Pick disease type C1. Conclusion As a precision medical tool, WGS enables a definitive diagnosis for some infants with genetic diseases and allows for early access to personalized treatment plans, thereby holding significant importance in the screening of genetic diseases.

Key words: whole genome sequencing, genetic disease, infants

摘要： 目的 探讨全基因组测序(WGS)技术在3月龄以下婴儿遗传性疾病筛查中的意义,为遗传性疾病精准诊断提供新方向。 方法 选取2019年4月—2024年4月首都医科大学附属北京儿童医院保定医院新生儿科病房临床诊断不明、怀疑遗传性疾病,且已行WGS分析的患儿为研究对象,收集临床资料,评估WGS技术在遗传性疾病中的意义。 结果 共纳入82例患儿,发现基因检测异常38例,检出率46.34%(38/82)。其中Gilbert综合征3例,大疱性表皮松解症2例,Coffin-Siris综合征2例,Prader Willi/Angelman综合征2例,甲基丙二酸尿症mut(0)型2例,甲基丙二酸尿症伴同型半胱氨酸尿症CblC型2例,其他还有:Sjogren-Larsson综合征、枫糖尿病2型、中枢性巨人症综合征2型、Neurofibromatosis-Noonan 综合征/神经纤维瘤病1型、Marshall综合征、X连锁先天性肾上腺发育不全、Treacher Collins综合征1型、多发性先天性畸形-张力减退-癫痫综合征、常染色体显性皮肤松弛症1型、先天性中枢性低通气综合征、脊肌萎缩症2型、16p11.2缺失综合征, 220kb、扩张型心肌病1CC型、11q23.3q25拷贝数重复、Kabuki综合征2型、Menkes病、线粒体DNA突变、着色性干皮病、免疫缺陷104型、少汗性外胚层发育不良症、婴儿期泛发性动脉钙化、新生儿重症脑病、G6PD缺乏性溶血性贫血、CHARGE综合征、尼曼-匹克病C1型各1例。 结论 WGS作为一种精准医疗手段,使部分遗传性疾病患儿明确诊断,尽早获取个性化治疗方案,在遗传性疾病筛查中具有重要意义。

关键词: 全基因组测序, 遗传性疾病, 婴儿