Xu Xilin, He Wenbin, Wang Ying, Gong Fei, Lu Guangxiu, Lin Ge, Tan Yueqiu, Du Juan
College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Mar 10;39(3):269-275. doi: 10.3760/cma.j.cn511374-20210318-00245.
To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age.
A total of 897 unrelated healthy individuals (including 143 couples) were recruited, and DNA was extracted from their peripheral blood samples. Whole exome sequencing (WES) was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases. Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed.
One hundred fourty types of pathogenic/likely pathogenic variants (with an overall number of 183) and unreported loss-of-function variants were detected, which yield a frequency of 0.20 per capita. A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis. The detected variants have involved 40 genes, with the most common ones including ATP7B, SLC25A13, PAH, CBS and MMACHC. Based on the Hardy-Weinberg equilibrium, the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100, with the five diseases with higher incidence including citrullinemia, methylmalonic acidemia, Wilson disease, glycogen storage disease, and phenylketonuria.
This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age, which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases. Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.
确定中国育龄人群中21种遗传性代谢疾病的携带率。
共招募了897名无亲缘关系的健康个体（包括143对夫妇），并从他们的外周血样本中提取DNA。进行全外显子组测序（WES）以筛选与21种遗传性代谢疾病相关的54个基因中的潜在变异。分析致病性和可能致病性变异以及未报告的功能丧失变异。
检测到140种致病性/可能致病性变异（共183个）以及未报告的功能丧失变异，人均频率为0.20。发现一对夫妻均携带SLC25A13基因的致病性变异，并在植入前基因诊断的帮助下生下了一个健康的婴儿。检测到的变异涉及40个基因，最常见的包括ATP7B、SLC25A13、PAH、CBS和MMACHC。基于哈迪-温伯格平衡，该人群中21种遗传性代谢疾病的发病率约为1/1100，发病率较高的五种疾病包括瓜氨酸血症、甲基丙二酸血症、威尔逊病、糖原贮积病和苯丙酮尿症。
本研究初步确定了中国育龄人群中21种遗传性代谢疾病的携带率和发病率，为遗传性代谢疾病新生儿筛查项目的设计提供了有价值的信息。孕前携带者筛查可为预防人群中孟德尔疾病的传播提供重要措施。
