Abstract
Germline mosaicism should be suspected when the same de novo mutations are identified in a second pregnancy with asymptomatic parents. Our study aims to find a feasible approach to reveal the existence of germline mosaicism. Multiplex Ligation-dependent Probe Amplification was performed on a Duchenne muscular dystrophy affected pedigree to detect deletion mutations. Then gap-polymerase chain reaction was performed to amplify the breakpoints junction sequence. Droplet digital polymerase chain reaction was utilized to identify the mutation frequencies in healthy parents. The same deletion in the exon 51 of the dystrophin gene, which was 50,035 bp in size, was detected in the proband and the fetus but not in their parents. Droplet digital polymerase chain reaction analysis of peripheral blood samples revealed mutant alleles of 3.53% in maternal blood cells. We here report a case of maternal low-level mosaicism confirmed by droplet digital polymerase chain reaction in peripheral blood samples, which reveals the existence of germline mosaicism. Gap-polymerase chain reaction combined with droplet digital polymerase chain reaction provide insights into the detection of germline mosaicism.
Highlights
De novo mutations (DNMs) refer to genetic changes in the offspring that cannot be detected in the genome of either parent (Haldane, 2004; Wilfert et al, 2017)
Cautions should be taken when the same DNMs repeatedly occur in two or more offspring: germline mosaicism might be the possible explanation of it (Bakker et al, 1987; Campbell et al, 2014; Di Donato et al, 2014; Patel et al, 2018; Qian et al, 2019)
Germline mosaicism is theoretically accompanied by low-level somatic mosaicism
Summary
De novo mutations (DNMs) refer to genetic changes in the offspring that cannot be detected in the genome of either parent (Haldane, 2004; Wilfert et al, 2017). Cautions should be taken when the same DNMs repeatedly occur in two or more offspring: germline mosaicism might be the possible explanation of it (Bakker et al, 1987; Campbell et al, 2014; Di Donato et al, 2014; Patel et al, 2018; Qian et al, 2019). Germline mosaicism is theoretically accompanied by low-level somatic mosaicism. The evidences above indicate that the identification of low-level somatic mutations is an efficient way to reveal the existence of germline mosaicism (Patel et al, 2018). The application of ddPCR makes it a reality to identify low-level mosaicism. The application of ddPCR to identify low-level mosaicism has provided insights into germline mosaicism
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