海南省少数民族地区新生儿遗传代谢病基因突变特征

目的 调查海南省少数民族地区新生儿人群遗传代谢病的发病情况和基因突变特征。方法 借助海南省新生儿疾病筛查网络收集2016年1月—2019年12月在海南省少数民族地区出生的新生儿共54 506例新生儿干血斑,使用串联质谱法检测干血斑中11项氨基酸、1项游离肉碱以及30项酰基肉碱的浓度,计算出相互间比值,共计78个代谢指标,进行多种遗传代谢病的初步筛查。筛查可疑病例重新釆血外送基因测序确诊。结果 在54 506例新生儿干血斑中确诊了24例遗传代谢性疾病,初步计算出海南省新生儿多种遗传代谢病的发病率为0.044%（24/54 506）,共发现12个遗传代谢病相关基因发生突变：PAH、SLCC22A5、MAT1A、PTS、ACADVL、PCCA、IVD、MCCC1、ARG1、MLYCD、MMAA和ASL,其中SLCC22A5占总基因突变的41.7%,在这11个基因中总计有28个位点发生了突变。结论 多种遗传代谢性疾病在海南省少数民族地区新生儿人群发病率高,突变基因类型丰富,且以SLCC22A5基因为主,因此有必要在海南省少数民族地区开展新生儿多种遗传代谢病的检测,以提高海南省该地区的出生人口素质。

Gene mutation for inherited metabolic diseases among the newborn population of Hainan minority areas

Objective To investigate the incidence and gene mutation characteristics of genetic inherited metabolic diseases among newborn babies in Hainan minority areas. Methods The neonatal dried blood samples were collected from 54 506 cases of newborns were born in ethnic minority areas of Hainan province from January 2016 to December 2019 through Hainan newborn disease screening network. Tandem mass spectrometry (MS/MS) was used to detect the concentration of 11 amino acids and 1 free carnitine 30 acylcarnitine in the dry blood spots, and a total of 78 metabolic indexes were determined by their ratios. The suspected samples were confirmed by re-sequencing of the extraneous DNA. Results A total of 24 cases of genetic metabolic diseases were confirmed in 54 506 cases of neonatal dry blood spots, with the incidence of inherited metabolic diseases of 0.044% (24/54 506) among newborns in Hainan province. In this study, The total of 11 genetic inherited metabolic diseases were found, including PAH, SLCC22A5, MAT1A, PTS, ACADVL, PCCA, IVD, MCCC1, ARG1, PCCA and MMAA. SLCC22A5 accounted for 41.7% of the total gene mutations in the inherited metabolic diseases. There were 28 mutated loci in 11 genes. Conclusion There is a high incidence of inherited metabolic diseases among newborns in the minority areas of Hainan province. The types of inherited metabolic diseases are abundant, and SLCC22A5 is the most common mutated gene. Therefore, in order to improve the quality of the newborn population in Hainan province, it is necessary to carry out the detection of inherited metabolic diseases in newborns in the minority areas of Hainan province.