Wang Huizi, Zhao Quxi, Xie Dongping, Peng Jinbi, Chen Guixian, Dong Xudong
The Obstetrical Department, The First People's Hospital of Yunnan Province, No. 157 Jinbi Road, Xishan District, Kunming, 650032, Yunnan Province, China.
The Obstetrical Department, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Sci Rep. 2025 Jul 2;15(1):23590. doi: 10.1038/s41598-025-08012-3.
Rare genetic diseases are responsible for a small but significant proportion of childhood morbidity and mortality. The majority of these diseases have no treatment and they create a huge burden on the families and the whole society. A well-tested strategy to prevent these diseases from happening is carrier screening, which can reduce the incidents of autosomal recessive (AR) and X-linked (XL) conditions. Using a carrier screening panel based on next-generation sequencing, 1265 patients including 388 pairs of couples were tested for 486 genes, covering 623 conditions. A total of 1397 variants were found in 66.32% of the individuals, representing a mutation burden of 1.10 variants per person. The highest mutation burdens were found in the subgroups participants with histories of abnormal pregnancies (1.38), health issues (1.34), and ultrasound anomalies(1.23), respectively. Among the 388 pairs of couples, 19 pairs were found to be at high risk of having a child affected by either AR (9 pairs) or XL (10 pairs) conditions. DUOX2, HBA1/2, and USH2A were the most frequently mutated genes found. A cutoff gene frequency of over 1/200 as recommended by ACMG in this study would include the top 20 genes and cover 37.94% of all the variants identified. Ten couples with fertility risk were followed up on their subsequent reproductive choices and intervention, including to choose IVF, abortion and keep the affected child. Given that most individuals carried 1 or 2 variants in this population, carrier screening programs seem to be a worthy investment as a public health tool. Patient follow-ups demonstrated that couples in China have diverse opinions and values regarding reproductive choices.
罕见遗传病在儿童发病率和死亡率中所占比例虽小但意义重大。这些疾病大多无法治疗，给家庭和整个社会带来了巨大负担。一种经过充分验证的预防这些疾病发生的策略是携带者筛查，它可以减少常染色体隐性（AR）和X连锁（XL）疾病的发生率。使用基于下一代测序的携带者筛查面板，对1265名患者（包括388对夫妇）进行了486个基因的检测，涵盖623种疾病。在66.32%的个体中总共发现了1397个变异，每人的突变负担为1.10个变异。在有异常妊娠史（1.38）、健康问题（1.34）和超声异常（1.23）的亚组参与者中发现了最高的突变负担。在388对夫妇中，发现有19对夫妇生育受AR（9对）或XL（10对）疾病影响孩子的风险较高。DUOX2、HBA1/2和USH2A是最常发现的突变基因。本研究中美国医学遗传学与基因组学学会（ACMG）推荐的超过1/200的截止基因频率将包括前20个基因，覆盖所有已鉴定变异的37.94%。对10对有生育风险的夫妇的后续生殖选择和干预进行了跟踪，包括选择体外受精、堕胎和留下患病儿童。鉴于该人群中的大多数个体携带1个或2个变异，携带者筛查计划作为一种公共卫生工具似乎是一项值得投资之举。患者随访表明，中国夫妇在生殖选择方面有不同的观点和价值观。
