Abstract
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.
Highlights
The demand for prenatal diagnosis (PD) for inherited genetic diseases is dramatically increasing because the number of known disease genes is growing and because the procedures for prenatal diagnoses (PDs) are becoming more effective
We found one case in which a technical error led to PD of carrier in two siblings that were born affected by cystic fibrosis (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 that caused hemophilia in a child that PD had revealed as healthy
In our Centre, that is the reference laboratory for molecular diagnostics of genetic diseases in Campania Region (Southern Italy, about 5 million inhabitants), we offered about 1200 PD for 73 different inherited diseases in 2013 [2], and the figure has increased to about 1500 PD for 120 different
Summary
The demand for prenatal diagnosis (PD) for inherited genetic diseases is dramatically increasing because the number of known disease genes is growing and because the procedures for PD are becoming more effective. Non-invasive PD can be used to determine fetal sex, aneuploidies, and micro-deletions, but it can be applied to PD for inherited genetic diseases only in autosomal recessive diseases when parental mutations are different [1]. Most PD for inherited genetic diseases is performed testing. In our Centre, that is the reference laboratory for molecular diagnostics of genetic diseases in Campania Region (Southern Italy, about 5 million inhabitants), we offered about 1200 PD for 73 different inherited diseases in 2013 [2], and the figure has increased to about 1500 PD for 120 different. Among the requests for PD of inherited genetic diseases, one of the most frequent is cystic fibrosis (CF) [3], an autosomal recessive disease due to about 2000 different mutations in the gene encoding the CF transmembrane regulator (CFTR)
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