Application and the limitation of next generation sequencing for the diagnosis of methylmalonic acidemia

OBJECTIVE To identify genetic variants among patients with methylmalonic acidemia and provide genetic evidence for prenatal diagnosis. METHODS Thirty-one probands and their parents were subjected to next generation sequencing (NGS). Suspected variants were verified by Sanger sequencing. RESULTS 25 probands or their parents were found to harbor previously known pathogenic or likely pathogenic variants, and three probands were found to carry heterozygous MMACHC exonic deletion. The overall diagnostic yield was 90.32%. CONCLUSION NGS can improve the detection rate for methylmalonic acidemia for its accuracy and efficiency, yet the detection of exonic deletion is required to further improve the diagnostic yield. The identification of specific variants provided evidence for prenatal diagnosis.