Single-Molecule Counting for Noninvasive Prenatal Diagnosis of Autosomal Recessive Hearing Loss in at-Risk Families: A Proof-of-Concept Study.

Identifying the molecular causes of hereditary sensorineural hearing loss is essential for effective prevention and control. Current prenatal diagnostic methods are primarily invasive and carry significant risks. While noninvasive prenatal testing for common aneuploidies has become widespread over the past decade, noninvasive prenatal testing for monogenic hereditary disorders remains limited by complex procedures, low detection accuracy, and the need for prior knowledge of parental genotypes or haplotypes. This study aimed to address these limitations. A noninvasive prenatal testing method for hereditary sensorineural hearing loss using next-generation sequencing based on single-molecule counting technology was developed. In a validation experiment involving 50 patients with singleton pregnancies at risk for fetal sensorineural hearing loss, the consistency and accuracy of allele detection for diagnosis were 99.67% and 96%, respectively. Single-molecule counting technology enabled relatively accurate identification of maternal and fetal genotypes from cell-free DNA. However, due to the limited sample size, reliable false-negative and false-positive rates could not be established. Thus, this study serves only as preliminary proof of concept for this detection method.