Prenatal diagnosis for
            de novo
            mutations: Experience from a tertiary center over a 10‐year period

Abstract Background Relative haplotype dosage (RHDO) approach has been applied in noninvasive prenatal diagnosis (NIPD) of Duchenne muscular dystrophy (DMD). However, the RHDO procedure is relatively complicated and the parental haplotypes need to be constructed. Furthermore, it is not suitable for the diagnosis of de novo mutations or mosaicism in germ cells. Here, we investigated NIPD of DMD using a relative mutation dosage (RMD)-based approach—cell-free DNA Barcode-Enabled Single-Molecule Test (cfBEST), which has not previously been applied in the diagnosis of exon deletion. Methods Five DMD families caused by DMD gene point mutations or exon deletion were recruited for this study. After the breakpoints of exon deletion were precisely mapped with multiple PCR, the genotypes of the fetuses from the five DMD families were inferred using cfBEST, and were further validated by invasive prenatal diagnosis. Results The cfBEST results of the five families indicated that one fetus was female and did not carry the familial molecular alteration, three fetuses were carriers and one was male without the familial mutation. The invasive prenatal diagnosis results were consistent with those of the cfBEST procedure. Conclusion This is the first report of NIPD of DMD using the RMD-based approach. We extended the application of cfBEST from point mutation to exon deletion mutation. The results showed that cfBEST would be suitable for NIPD of DMD caused by different kinds of mutation types.

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Genome-Wide Noninvasive Prenatal Diagnosis of De Novo Mutations

Methods in Molecular Biology - Deep Sequencing Data Analysis ◽

10.1007/978-1-0716-1103-6_12 ◽

2021 ◽

pp. 249-269

Author(s):

Ravit Peretz-Machluf ◽

Tom Rabinowitz ◽

Noam Shomron

Keyword(s):

Prenatal Diagnosis ◽

De Novo ◽

De Novo Mutations ◽

Noninvasive Prenatal Diagnosis ◽

Genome Wide

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Prenatal Diagnosis of Cystic Fibrosis and Hemophilia: Incidental Findings and Weak Points

Diagnostics ◽

10.3390/diagnostics10010007 ◽

2019 ◽

Vol 10 (1) ◽

pp. 7 ◽

Cited By ~ 1

Author(s):

Marika Comegna ◽

Giuseppe Maria Maruotti ◽

Laura Sarno ◽

Gustavo Cernera ◽

Monica Gelzo ◽

...

Keyword(s):

Cystic Fibrosis ◽

Prenatal Diagnosis ◽

Incidental Findings ◽

De Novo ◽

Genetic Diseases ◽

Legal Aspects ◽

De Novo Mutation ◽

De Novo Mutations ◽

Weak Points ◽

Genetics And Genomics

Because of the progression of genetics and genomics, the demand for prenatal diagnosis (PD) for inherited genetic diseases has increased. However, several incidental findings may emerge during PD, like misattributed paternity, the evidence of disease in a parent, and the possible misinterpretation of the results because of complex alleles or de novo mutations that have several implications. In a retrospective observational study on all the couples referred to our Medical School (1993–2018) for PD of genetic inherited diseases (n = 1502), we selected the cases of PD for cystic fibrosis (CF, n = 239) and hemophilia A and B (HA, HB, n = 47), revising all incidental findings previously mentioned. We found one case in which a technical error led to PD of carrier in two siblings that were born affected by CF, four cases of misattributed paternity, eight cases of asymptomatic parents revealed as affected by CF transmembrane regulator (CFTR)-related disorders, a case of a novel complex allele that could have caused the diagnosis of CF in a carrier fetus, and a case of a de novo mutation in a mother (already a carrier) that caused hemophilia in a child that PD had revealed as healthy. We present these conditions as clinical cases and discuss the technical, clinical, ethical, and legal aspects to be considered.

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