Fetal structural anomalies are found in up to 3 % of all pregnancies following routine ultrasound screening (Edwards and Hui, 2017, PMID: 29233624). A diagnosis is difficult due to limited phenotypic information, but it is crucial to gain information about disease prognosis. The prenatal exome analysis assists in such cases by identifying the genetic cause of the disease. The Prenatal ExomeXtra® can also be performed if prenatal ultrasound examinations are inconspicuous. Diagnostic without abnormal ultrasound findings examines more than 2,000 genes associated with severe, early-onset diseases.
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What We Offer with This Service
Our Promise to You
Medical Report With:
- Variants with phenotypical relevance (ACMG class 4,5)
- Interpretation & discussion of these variants and the affected genes
- Interpretation of genetic relevance for family planning
- Detection of copy number variants (CNV) – more information
Additional Diagnostic Services (for the Parents):
- ACMG gene panel – more information
- Pharmacogenetics – more information
- HLA typing – more information
Our Standard Sample Requirements
For the Fetus:
- Amniotic fluid (native or cultured)
- Chorionic villi (native or cultured)
- Extracted fetal DNA
- Abortion material
For the Parents:
- 1-2 ml EDTA blood (recommended sample type)
- Genomic DNA (1-2 µg)
- DBS cards, buccal swabs, or saliva are also possible
Here you can find more information on how to ship your sample safely.
If prenatal trio exome diagnostics is not possible, we still need a sample from the mother to test for maternal cell contamination (MCC). Other sample material sources are possible on request. Please note: In case of insufficient sample quality, the analysis might fail. If you have more than one option of samples, please contact us (firstname.lastname@example.org), and we will assist you in choosing the optimal sample for your patient.
Prenatal Diagnostics – With and without Abnormal Ultrasound Findings
The exomes of both parents and the index patient are sequenced to enable comparative analysis. Out of 500 analyses, we identified the disease-causing variation in 38 % by this method. (Gabriel et al., ESHG 2020, C01.6 Trio exome sequencing is highly relevant in prenatal diagnostics).
Diagnostics – With Conspicuous Ultrasound Findings:
The Prenatal ExomeXtra® is used to determine the genetic cause of a disease in a fetus with abnormal ultrasound findings. In addition, we investigate the risk of serious health complications in the early stages of a child’s life. The analysis of the exomes of the fetus and both parents (trio exome diagnostics) enables a comparative analysis and increases the probability of identifying disease-causing variants.
Prenatal ExomeXtra® diagnostics enable the detection of variants that affect metabolism, for example and offer the possibility of initiating treatment immediately after birth. Our unique analysis approach also allows the detection of variants with imprinting effects, variable expressivity, and reduced penetrance.
Diagnostics – Without Ultrasound Findings:
The Prenatal ExomeXtra® can also be performed if prenatal ultrasound examinations are inconspicuous. We have compiled a comprehensive panel of over 2,000 genes associated with severe early-onset diseases in cooperation with leading experts in prenatal clinical human genetics. After trio exome analysis and filtering, we screen all genes in the panel for pathogenic and likely pathogenic (ACMG class 4, 5) variants associated with severe, early-onset disease.
Our expert committee discusses and reports pathogenic and likely pathogenic variants outside this gene panel regarding their effects on the fetus if they lead to severe early childhood fetal disorders. In this way, we consider the latest scientific findings at all times.
Extra Insightful Results
The human exome contains all protein-coding regions (exons) of about 23,000 genes in the genome. The exome makes up only about 1-2 % of the whole genome, but close to 89 % of all known disease-causing mutations to be located within the exons. Our proprietary design also covers more than 33,500 non-coding variants described as disease-relevant in the databases HGMD and ClinVar. In addition, we screen for the risk of severe health complications in the early stages of a child’s life. The exomes of the parents and the index patient are sequenced, allowing a comparative analysis. Get further information of Trio ExomeXtra® here. The additional screening for variants outside the phenotype described enables the detection of variants that affect metabolism, for example, with the possibility of intervening immediately after birth.
Our Unique Analysis Strategy Considers Often Overlooked Issues, Such as Mildly Affected Parents
Standard trio exome diagnostics assumes that both parents are not affected. This filtering ignores that some parents are only mildly affected, for example, which would result in negative findings. We compensate for these situations with a unique analysis strategy that allows us to solve cases where the phenotype is caused by variants with
- imprinting effects
- variable expressivity
- reduced penetrance
In addition, variants in the mitochondrial genome are evaluated when the phenotype indicates the possibility of a mitochondrial disease. In the case of prenatal diagnostics, the analysis of mtDNA is always included.
Study: Prenatal Trio Exome Sequencing Clarifies Ultrasound Abnormalities with a Solution Rate of 38%. Continue reading
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Identifiy the disease-causing alteration in a fetus
Do you have a question, or are you interested in our service?
We will assist you in selecting the diagnostic strategy – for each patient.