Noninvasive Prenatal Diagnosis of Duchenne Muscular Dystrophy: Comprehensive Genetic Diagnosis in Carrier, Proband, and Fetus

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.

Development of novel noninvasive prenatal testing protocol for whole autosomal recessive disease using picodroplet digital PCR

“…Yoo et al . reported that the lowest cffDNA fraction allowing successful NIPT with MPS was 5.8%29. Although New et al .…”

“…First, the biggest difference is that MPS deducts the fetal haplotypes through sequencing numerous SNPs around the residue of interest2526272829. Conversely, our method sequences a residue of interest directly even if a mutation exists in a homozygous fashion.…”

CUGC for Duchenne muscular dystrophy (DMD)

“…Parents of boys with DMD typically seek medical attention for their child between the ages of 3 and 5 years [13], although prenatal [23], and newborn [24] testing is available to families with confirmed X-linked carrier status. The first postnatal diagnostic test is generally serum CK level, which is always elevated (usually between 50 and 100 times normal levels) [25].…”

Duchenne Muscular Dystrophy Diagnostics: It Only Gets Better but Some of the Same Challenges Remain

“…In this issue of Clinical Chemistry, Yoo and colleagues report a new tool in DMD diagnostics (8 ). In this feasibility study, the authors used fetal DNA from maternal plasma and parallel targeted deep sequencing for noninvasive prenatal diagnosis of DMD.…”

“…For even when the fetal DNA possesses the same haplotype as the proband, the fetus may not be affected because the proband may be the result of an isolated sporadic mutation. Thus it is imperative that the mutation identified in the proband be confirmed in the mother before the prenatal testing, which the authors did in all 4 cases [ Table 1 in the article (8 )]. However, even when the mutation is not found in the mother, she still has an uncertain risk of carrier status, owing to the possibility of germline mosaicism (9 ).…”