Noninvasive prenatal testing for single-gene disorders (NIPT-SGD) is promising in detecting autosomal dominant disorders, including Alagille syndrome (ALGS), researchers found in a newly published study.

Mohan et al retrospectively analyzed a cohort of 2208 pregnant women (≥9 weeks gestational age) who received NIPT-SGD. “NIPT-SGD involved sequencing of coding exons, and 10 bp exon/intron boundaries in DNA extracted from maternal plasma, maternal genomic DNA, and paternal genomic DNA (trio testing),” the study authors explained.

Out of the total number of cases included in this study, 125 (5.7%) tested positive for a single-gene disorder. No false-positive or false-negative results were found among cases with available confirmatory follow-up testing (65/125).

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The indications for testing included advanced paternal age (41.3%), abnormal ultrasound (23.3%), and family history (6%). The highest positivity rates were found in cases referred for testing due to fetal long bone abnormalities (33.7%), fetal skull/facial malformations (28.6%), family history (15.2%), fetal lymphatic abnormalities (13.3%), and fetal cardiac abnormalities (12.9%). Out of the 60 referrals with shortened or abnormal long bones at ultrasound examination whose test was positive, 1 test corresponded to ALGS.

The test used in this study, which was made available as a clinical service using the brand name of Vistara, examined a specific set of dominantly inherited or de novo gene variants in 30 genes. This covered a total of 25 disorders, including ALGS.

At present, noninvasive prenatal testing is commonly used to detect fetal chromosomal abnormalities. This testing is based on the detection of cell-free fetal DNA (cffDNA) in maternal plasma, which can be analyzed by next-generation sequencing.


Mohan P, Lemoine J, Trotter C, et al. Clinical experience with non-invasive prenatal screening for single-gene disorders (NIPT-SGD). Ultrasound Obstet Gynecol. Published online August 6, 2021. doi:10.1002/uog.23756