The technique of next-generation sequencing (NGS) has become very important in the prenatal situation, along with cytogenetics and microarray. Still, in case of an abnormal ultrasound after a diagnostic puncture, karyotyping is usually performed first. However, in order not to lose valuable time, it is advisable to initially check whether, based on the indication, a material assay should be considered for a promptly following NGS diagnostic (gene panel or trio exome analysis).
Our medical team is available for consultation and planning in individual cases: +49 (0)89 / 3090886 - 0
Gene panel in prenatal diagnostics
A gene panel is useful when a possible diagnosis based on the fetal phenotype, which can be based on changes in different genes, needs to be specifically detected or also ruled out with a high degree of certainty.
Defined gene panels that may be useful in the prenatal situation can be found on our Prenatal Medicine Request Form:
Significance of trio exome analysis:
In the case of developmental disorders manifesting early or already prenatally, there is a high probability of either a new mutation or a recessive disease. In both cases, when evaluating NGS analyses, it is helpful to know which gene alteration is not present in the parents (and is then a new mutation in the child) or is present (as a predisposing carrier for a recessive disease in both parents). It is therefore useful to perform comprehensive NGS analyses in a trio approach including parental blood samples. This reduces the number of unclear sequence variants and increases the diagnostic yield and safety.
Processing time
7-10 days from start of NGS analysis
Costs
A cost breakdown can be requested.
In case of a trio exome analysis, additional examination material of the parents is required for the analytical validation of the fetal variants (4ml EDTA blood each).
Further information - FAQs
Exome studies are performed as "Clinical Exomes", which include only genes with known disease association. The analysis of a "Whole Exome"- is not useful, because genetic alterations in genes that are not associated with a disease do not represent a diagnostic gain in the prenatal situation.
How are NGS data interpreted?
The goal of variant interpretation is to identify the cause of the abnormal fetal phenotype in order to provide the pregnant woman with a prognostic and, if necessary, therapeutic assessment. Accordingly, only variants that can be considered to explain the fetal phenotype with certainty or high probability at the current time are reported.
Which fetal material is suitable?
Exome analysis is possible from native amniotic fluid, CVS material, cell cultures, or even fetal cord blood.
How is contamination excluded?
Maternal contamination of fetal material can be detected or excluded using a bioinformatic analysis tool even without the presence of a blood sample from the pregnant woman.
Material prenatal
Molecular genetic testing is preferably performed from chorionic villi. The examination can be performed after DNA extraction of native chorionic villi. The minimum amount of chorionic villi should then be at least 15 mg.
Diagnostics from native amniotic fluid is also possible. The minimum volume of amniotic fluid is 5 ml (optimally 20ml) for pregnancies from 16 weeks of gestation.
If sufficient DNA of sufficient quality cannot be obtained from native amniotic fluid primarily, molecular genetic testing is performed after DNA extraction of the amniotic fluid cell culture. This requires a longer processing time.
AMNIOTIC FLUID
From gestational week (SSW) 14+0
Required (minimum to optimal) sample volume: 5 - 20 ml
CHORIONIC VILLI (CVS)
From gestational week (SSW) 11+0
Required (minimum to optimal) sample size: 5 - 30 mg
CELL CULTURES FROM AMNIOTIC FLUID / CHORIONIC VILLI
Confluent growing cell culture flask (T25)
Completely filled with nutrient solution
FETAL CORD BLOOD
EDTA blood for molecular genetic testing
Heparinized blood for cytogenetic and FISH studies
Required (minimum to optimal) sample volume: 0.5 - 4 ml
PARENTAL BLOOD SAMPLES
For analytical validation of possible gene variants of the fetus an EDTA blood sample of the parents is required in addition to the prenatal sample (2 - 4 ml each)
For analytical validation of chromosomal variants, a heparinized blood sample from the parents is required in addition to the prenatal sample (2 - 4 ml each)
MISCARRIAGE TISSUE
placental villi or fetal tissue
MATERNAL BLOOD (NIPT - Non-Invasive Prenatal Test / cfDNA).
General:
Please label each specimen tube with the patient's last name, first name, and date of birth.
Each sample submitted will be evaluated for DNA quality criteria (QC) prior to the start of analysis. If the quality is insufficient, we will request another material sample.