Integration of targeted sequencing and NIPT into clinical practice in a Chinese family with maple syrup urine disease.

Purpose: This article demonstrates a prominent noninvasive prenatal approach to assist the clinical diagnosis of a single-gene disorder disease, maple syrup urine disease, using targeted sequencing knowledge from the affected family.

Methods: The method reported here combines novel mutant discovery in known genes by targeted massively parallel sequencing with noninvasive prenatal testing.

Results: By applying this new strategy, we successfully revealed novel mutations in the gene BCKDHA (Ex2_4dup and c.392A>G) in this Chinese family and developed a prenatal haplotype-assisted approach to noninvasively detect the genotype of the fetus (transmitted from both parents).

Conclusion: This is the first report of integration of targeted sequencing and noninvasive prenatal testing into clinical practice. Our study has demonstrated that this massively parallel sequencing-based strategy can potentially be used for single-gene disorder diagnosis in the future.