Development and validation of a haplotype-free technique for non-invasive prenatal diagnosis of spinal muscular atrophy

Abstract

Objective: To develop a technique for non-invasive prenatal diagnosis of spinal muscular atrophy and validate its performance. Study Design: Pregnant women with 1 copy of SMN1 and male fetuses were enrolled. Seventeen women were included in test set A, and 10 of them were selected into test set B randomly and blinded. The two sets were tested independently by two different researchers blinded to fetal genotypes. Fetal DNA fractions were calculated based on the relative proportion of mapped chromosome Y sequencing reads. An algorithm was developed to decide fetal SMN1 copy numbers. Results: The concordance rate with the results of MLPA testing of amniocyte DNA was 94.12% in test set A and 90% in set B. For all tests with a classifiable result, the percent of agreement with the results of MLPA testing of amniocyte DNA was up to 100% (25/25). Conclusion: We have developed a direct, rapid, and low-cost technique, which has a potential to be utilized for first-trimester non-invasive prenatal diagnosis and screening for spinal muscular atrophy with considerable reliability and feasibility.