西藏山南地区新生儿遗传代谢性疾病及4个常见耳聋基因筛查结果分析

Newborn screening results for inherited metabolic disorders and four common deafness-associated genes in Shannan, Tibet, China

摘要

目的 分析西藏山南地区新生儿中48种遗传代谢病(IMD)及4种常见耳聋基因的突变情况,为高原地区新生儿遗传病的早期筛查和防控提供基础数据支持。方法 选取2021年12月15日—2022年12月31日期间在山南地区12家医疗机构出生的活产新生儿作为观察对象,对1 456名新生儿采用串联质谱分析检测氨基酸、有机酸和脂肪酸代谢物水平,1 497名进行了4个耳聋基因GJB2, GJB3, SLC26A4, MT-RNR1的20个常见位点的筛查,将筛查结果进行综合分析。结果 山南地区新生儿IMD初筛阳性率为1.79%(26/1 456)。从疾病种类来看,高苯丙氨酸血症(8例,占34.6%)最常见,1例疑似;其次为丙酸血症/甲基丙二酸血症(7例,占26.9%),原发性肉碱转运缺乏症(4例,占15.4%)。4个常见耳聋基因的20个常见位点的初筛阳性率为1.74%(26/1 497),MT-RNR1(12S rRNA)基因突变在本地区检出人数最多(14例,占53.8%),其次是GJB2基因(8例,占30.8%)。结论 山南地区新生儿IMD质谱筛查阳性率高于全国新生儿的筛查阳性率,也高于同属高原的青海地区筛查结果;4种常见耳聋基因携带率低于国内其它地区。本研究为高原地区新生儿筛查的策略优化及IMD防控提供参考。

Abstract

Objective To analyze the mutation profiles of 48 inherited metabolic disorders (IMDs) and 4 common deafness-associated genes among newborns in Shannan, Tibet, in order to provide baseline data for early screening and prevention of genetic diseases in high-altitude regions. Methods Live-born neonates delivered in 12 health service centers in the Shannan region between December 15, 2021, and December 31, 2022, were enrolled. Tandem mass spectrometry was performed in 1 456 newborns to measure amino acids, organic acids, and fatty-acid metabolites. In addition, 1 497 newborns were screened for 20 common variants in four deafness-associated genes (GJB2, GJB3, SLC26A4, and MT-RNR1). Screening results were summarized descriptively. Results The initial positive screening rate for IMDs was 1.79% (26/1 456), covering nine categories of suspected IMDs/abnormal screening profiles. Hyperphenylalaninemia (8 cases, 34.6%, including 1 suspected case) was the most prevalent, followed by propionic acidemia/methylmalonic acidemia (7 cases, 26.9%) and primary carnitine transporter deficiency (4 cases, 15.4%). The positive screening rate for the four deafness genes was 1.74% (26/1 497). MT-RNR1 variants were the most frequent (14 cases, 53.8%), followed by GJB2 variants (8 cases, 30.8%). Conclusions The initial positive rate of IMD screening in Shannan is higher than the national average and reported in Qinghai, another plateau region of China, and the carrier rate of common deafness genes is lower than the national average. This study provides a scientific reference for optimizing newborn screening strategies and preventing genetic diseases in high-altitude regions.

关键词

遗传代谢性疾病 / 耳聋基因 / 新生儿疾病筛查 / 高原地区

Key words

inherited metabolic disorders / deafness gene / newborn screening / high-altitude areas

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基金资助

山南市本级科技计划项目(SNSBJKJJHXM2023013);长江大学医学部科技援藏“医卫人才培养计划项目”(2023YZ01)