Trio ExomeXtra® is used to diagnose an affected patient with unaffected parents. Including both unaffected parents in the analysis significantly increases the chances of a successful diagnostics. The exome encompasses all protein-coding regions (exons) of the about 23,000 genes in the human genome. Although the exome accounts for only about 1-2 % of the whole genome, approximately 89 % of all known disease-causing mutations are located within the exons. Our proprietary exome design additionally covers more than 28,500 non-coding variants described as disease-relevant in the HGMD and ClinVar databases.
For Trio ExomeXtra®, the exomes of the parents and the index patient are sequenced. This allows an exome-wide segregation analysis and, thus, the highest solution rates. Comparative exome diagnostics is particularly effective because the number of variants to be evaluated is minimized, and single variants’ numerous and cost-intensive segregation analyses are avoided.
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What We Offer with This Service
Our Promise to You
Service Details
Medical Report with:
- Variants with phenotypical relevance (ACMG class 3,4,5) – more information
- Interpretation & discussion of these variants and the affected genes
- Interpretation of genetic relevance for family planning
- Recommendations for clinical disease management & further tests
- Detection of copy number variants (CNV) – more information
Additional Services:
- ACMG gene panel – more information
- Pharmacogenetics – more information
- HLA typing – more information
Sample Report
Our Standard Sample Requirements
- 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.
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 (diagnostic-support@cegat.de) and we will assist you in choosing the optimal sample for your patient.
Benefit From Our Comparative ExomeXtra®
In comparative family exome diagnostics, not only the affected patient but also other relatives are sequenced. The most commonly performed analysis is the trio exome: The inclusion of both unaffected parents of the index patient highly increases the chances of diagnostic success to be approximately twice as high compared to single exome diagnostics (Farwell et al., 2015).
In family constellations where it is not possible to obtain a sample from both genetic parents, or one parent might be affected as well, the adaptive ExomeXtra® bioinformatic pipeline allows us to analyze all kinds of family combinations, like duos.
This goes beyond commonly performed analyses of private and shared variants between two persons. Our additional analyses are the best approach for solving cases with only one parent (affected or unaffected) or any other index-relative constellations. A detailed phenotypic description of all affected individuals is the basis for a precise and successful data interpretation.
In the evaluation process, our experienced team investigates all variants according to the latest clinical knowledge.
For variants in genes that are not clearly associated, with the patient’s suspected phenotype, we predict the possible contribution through extensive additional literature research. If we find evidence that a variant not yet described contributes to the patient’s phenotype, this variant is described in our medical report. Comparison of the affected patient’s data with those of the unaffected parents allows us to identify the following SNV/CNV combinations:
- De novo – new in the index, not present in parents
- Homozygous – homozygous in the index, heterozygous in both parents
- Compound heterozygous – two or more variants in the same gene in the index on different alleles; each parent is a heterozygous carrier of one variant
- X-linked – male patient is hemizygous, the mother is heterozygous
- Loss of heterozygosity – index is homozygous, one parent heterozygous, other parent wildtype
- Parental mosaicism – index is heterozygous, one parent has a genetic mosaicism
Extra Insightful Results
Our Unique Analysis Strategy Considers Often Overlooked Issues, Such as Mildly Affected Parents
Standard trio exome diagnostics rely on the assumption 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:
- reduced penetrance
- variable expressivity
- imprinting effects
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.
Further Information
Webinar: Better than exome, smarter than genome
Dr. Dr. Saskia Biskup about ExomeXtra®
Trio exome diagnostics: One of the most powerful tools in genetic diagnostics
Designing the best possible exome
Identifiy the disease-causing alteration in a fetus
Exome diagnostics saved a little girl’s life
Case report: Saving a little girl‘s life.
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Diagnostic Support
We will assist you in selecting the diagnostic strategy – for each patient.
