Abstract
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.