Noninvasive prenatal test for FGFR3‐related skeletal dysplasia based on next‐generation sequencing and plasma cell‐free DNA: Test performance analysis and feasibility exploration

Abstract

Our method had a favorable performance for noninvasively detecting fetal FGFR3 mutations in maternal plasma, highlighting its promising value in developing a noninvasive prenatal test for de novo and paternally inherited disorders.

A sonographic approach to the prenatal diagnosis of skeletal dysplasias

“…This further emphasises the need to involve the clinical geneticist in the prenatal evaluation of these conditions. For achondroplasia, thanatophoric dysplasia, and Apert syndrome, as well as selected other syndromes, definitive molecular diagnosis can be achieved using NIPD and analysis of cell‐free DNA in maternal blood . Of greater potential utility, but requiring invasive testing, is exome sequencing, which has the ability to screen affected pregnancies for multiple mutations in many genes, thereby increasing the possibility of arriving at a definitive diagnosis in a timely fashion in pregnancy.…”

“…39 Both 2D and 3D ultrasonography have limitations in the presence of a high maternal body mass index, excessive fetal movements and thoracic shadowing, particularly at later gestational ages. These limitations can to some extent be [44][45][46] Of greater potential utility, but requiring invasive testing, is exome sequencing, which has the ability to screen affected pregnancies for multiple mutations in many genes, 47 thereby increasing the possibility of arriving at a definitive diagnosis in a timely fashion in pregnancy. Exome sequencing with variant interpretation focused on a virtual panel of genes known to cause skeletal dysplasias has been shown to have a diagnostic yield as high as 83% in fetuses suspected of having a skeletal dyplasia.…”

Simultaneous detection of fetal aneuploidy, de novoFGFR3 mutations and paternally derived β‐thalassemia by a novel method of noninvasive prenatal testing

“…[4][5][6] Recently, noninvasive detection of the de novo mutations causing certain autosomal dominant disease has been determined to have clinical significance. 7 Meanwhile, several studies have demonstrated the detection of fetal monogenic diseases by analyzing cfDNA using quantitative polymerase chain reaction (qPCR), digital PCR, or haplotype-assisted approaches. [8][9][10][11][12][13] The detection of monogenic diseases with such methods provides the full genotype assessment of fetus, and certain method such as the haplotype-based approaches can even interpret the inheritance of the maternal allele.…”

In case you missed it: The prenatal diagnosis editors bring you the most significant advances of 2018

“…Remarkably, 70% of the tests to date have been done on Chinese women. While the majority of cell‐free DNA tests are performed for the common fetal autosomal and sex chromosome aneuploidies, the test menus have expanded to include microdeletions, copy number variations, and single gene disorders . In an extraordinary study published in October 2018, Liu and colleagues performed a large‐scale population analysis using shallow sequencing data from 141 431 NIPTs performed at the Beijing Genome Institute in Shenzhen .…”