Noninvasive prenatal diagnosis of Duchenne muscular dystrophy: Comprehensive genetic diagnosis in carrier, proband, and fetus

Seong Keun Yoo, Byung Chan Lim, Jiyoung Byeun, Hee Hwang, Ki Joong Kim, Yong Seung Hwang, Joon Ho Lee, Joong Shin Park, Yong Sun Lee, Junghyun Namkung, Jungsun Park, Seungbok Lee, Jong Yeon Shin, Jeong Sun Seo, Jong Il Kim, Jong Hee Chae

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30 Citations (Scopus)

Abstract

BACKGROUND: Noninvasive prenatal diagnosis of monogenic disorders using maternal plasma and targeted massively parallel sequencing is being investigated actively. We previously demonstrated that comprehensive genetic diagnosis of a Duchenne muscular dystrophy (DMD) patient is feasible using a single targeted sequencing platform. Here we demonstrate the applicability of this approach to carrier detection and noninvasive prenatal diagnosis. METHODS: Custom solution-based target enrichment was designed to cover the entire dystrophin (DMD) gene region. Targeted massively parallel sequencing was performed using genomic DNA from 4 mother and proband pairs to test whether carrier status could be detected reliably. Maternal plasma DNA at varying gestational weeks was collected from the same families and sequenced using the same targeted platform to predict the inheritance of the DMD mutation by their fetus. Overrepresentation of an inherited allele was determined by comparing the allele fraction of 2 phased haplotypes after examining and correcting for the recombination event. RESULTS: The carrier status of deletion/duplication and point mutations was detected reliably through using a single targeted massively parallel sequencing platform. Whether the fetus had inherited the DMD mutation was predicted correctly in all 4 families as early as 6 weeks and 5 days of gestation. In one of these, detection of the recombination event and reconstruction of the phased haplotype produced a correct diagnosis. CONCLUSIONS: Noninvasive prenatal diagnosis of DMD is feasible using a single targeted massively parallel sequencing platform with tiling design.

Original languageEnglish
Pages (from-to)829-837
Number of pages9
JournalClinical Chemistry
Volume61
Issue number6
DOIs
Publication statusPublished - 2015 Jun 1

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Biochemistry, medical

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    Yoo, S. K., Lim, B. C., Byeun, J., Hwang, H., Kim, K. J., Hwang, Y. S., Lee, J. H., Park, J. S., Lee, Y. S., Namkung, J., Park, J., Lee, S., Shin, J. Y., Seo, J. S., Kim, J. I., & Chae, J. H. (2015). Noninvasive prenatal diagnosis of Duchenne muscular dystrophy: Comprehensive genetic diagnosis in carrier, proband, and fetus. Clinical Chemistry, 61(6), 829-837. https://doi.org/10.1373/clinchem.2014.236380