Fig. 3

Prenatal genetic testing with workflow and outcome of pregnancies with previously identified disease-causing variant. Families with 101 pregnancies presented at < 16 gestational weeks (GW) from 2013 through 2017. Of these, 17 declined prenatal diagnostics after risk-to-benefit assessment. Diagnostic decision support software (DDSS) was applied to verify the molecular diagnosis and confirmed the relationship between genotype and phenotype in the remaining 84 pregnancies that received amniocentesis at 14–16 GW for targeted fetal genotyping. Of these, 24 tested positive and 60 tested negative for the biallelic disease-causing variant. Eight of the 24 pregnancies that tested positive were carried to term, and in each case the child was diagnosed with a disease concordant with the older affected sibling or siblings. Of 60 pregnancies that tested negative, one spontaneous miscarriage was excluded from evaluation, and 59 pregnancies were carried to term. In each of these 59 cases, the child was unaffected at birth and remained unaffected by the time of the last clinical follow-up for the tested disorder. Binomial goodness-of-fit test showed statistically significant difference in the primary outcome measure (95% CI, 0.04 to 0.20; P = .011) (n - number of individual pregnancies)