Whole Genome Sequencing
CentoGenome® – It’s Covered
One of the world’s most comprehensive tools for the diagnosis of rare and neurodegenerative diseases – providing unparalleled genome coverage and diagnostic power in a single test.
CENTOGENE’s Whole Genome Sequencing Service
Establishing a rapid and reliable diagnosis for rare and neurodegenerative diseases can be difficult, even for the most skilled physicians. However, with the latest advancements in technology, the utilization of Whole Genome Sequencing (WGS) as a first-line diagnostic test, and our deepening understanding of genetic factors, this challenge is now more manageable than ever before.
CENTOGENE’s enhanced WGS solution, CentoGenome, stands as one of the world’s most comprehensive tools for diagnosing rare and neurodegenerative diseases, providing unparalleled genome coverage and diagnostic power in a single test. This cutting-edge solution combines superior technology driven by a streamlined CE-IVD bioinformatics pipeline and medical expert-based interpretation using CENTOGENE’s Biodatabank. CentoGenome can detect nearly all variant types, from sequence variants to more complex variations such as copy number variations, uniparental disomy, and repeat expansions, in a single test.
With CentoGenome, you can significantly reduce time and resources to deliver a rapid and reliable diagnosis and identification of treatment options for your patients.
Why Choose CentoGenome?
Advanced Technology for Greater Insights
By implementing Polymerase Chain Reaction (PCR)-free technology, CentoGenome significantly reduces bias and provides high-quality sequence information for difficult-to-sequence genetic regions – enabling greater insights into coding, regulatory, and intronic regions.
Integrated Variant Reclassification & Confirmatory Testing for a Life-Long Commitment
As a world leader and trusted partner, CENTOGENE provides a free-of-charge and proactive diagnosis confirmation and variant reclassification when necessary.
Superior Performance for Enhanced Disease Coverage
CentoGenome leverages advanced data analysis through our CE-IVD bioinformatics pipeline and medical expert-based interpretation, powered by the CENTOGENE Biodatabank, to deliver superior variant detection.
Superior Technology With Unparalleled Clinical Coverage
Serving as a first-line test, CentoGenome is one of the most comprehensive commercially available WGS tests on the market for both rare and neurodegenerative disorders – covering almost all disease-causing variants, including most known repeat expansions associated with neurological diseases, in a single assay1. CentoGenome also detects Copy Number Variations (CNVs) associated with Spinal Muscular Atrophy (SMA), as well as disease-causing variants associated with Gaucher Disease (GD) and susceptibility to GBA1-related Parkinson's Disease (PD), with the highest levels of sensitivity.
The newly designed WGS assay leverages a PCR-free approach. This significantly diminishes the typical bias induced by PCR and provides higher quality sequence data across the typically challenging regions of the genome by enabling more uniform coverage and superior performance in variant detection.
Key Features & Performance | |||||
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| Uniform Genome Coverage |
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| Advanced and Sensitive Variant Detection |
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| Enhanced Detection of Variants Associated to SMA & GD / PD*** |
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SNVs: single nucleotide variants; InDels: small insertions/deletions; SVs: Structural variants; CNVs: copy number variations; UPD: uniparental disomy; mtDNA: mitochondrial DNA
* Variants with low quality and / or unclear zygosity are confirmed by orthogonal methods: SNVs and InDels by Sanger sequencing; CNVs by Multiplex Ligation-Dependent Probe Amplification (MLPA), Quantitative Polymerase Chain Reaction (qPCR), or Chromosomal Microarray (CMA). Internal confirmatory testing using an orthogonal method is also guaranteed when necessary for reported variants associated with repeat expansion diseases, UPD, SMN1/SMN2 CNVs, and conversion events between GBA1 and GBAP1, respectively by Fragment Length Analysis (FLA), CMA, MLPA, and qPCR
** Screening of UPD is performed using an in-house algorithm for Mendelian Inheritance Errors (MIE) to detect Runs of Homozygosity (ROH) for the well-known clinically relevant chromosomal regions. Screening of repeat expansions is performed by the ExpansionHunter.
*** SMA screening is performed using SMN Caller algorithm to detect SMN1/SMN2 CNVs. GBA1 screening is performed using Gauchian algorithm to detect recombination events affecting the region encompassing exons 9–11 (NM_000157.3), a region which has the highest homology to GBAP1
When is WGS Recommended?
CentoGenome is the ideal solution for diagnosing rare and neurodegenerative diseases. It serves as a first-line test to establish a molecular diagnosis in patients with suspected genetic disorders, or as a second-line test for patients with negative results from previous genetic testing. CentoGenome offers a potentially cost-effective alternative to establish a molecular diagnosis compared to performing multiple independent molecular assays.
Recent studies and Medical Genetic Society Statements and Recommendations on clinical WGS support it as a first- or second-line diagnostic test when a patient’s symptoms or family history suggests a genetic cause of diseases.2–6 This is especially the case when the clinical diagnosis is associated with a high level of genetic heterogeneity and when WGS results in a relevant clinical improvement and/or is a more cost-effective approach. For example, the American College of Medical Genetics and Genomics (ACMG) recommends the use of exome/genome sequencing as first-tier tests for children with intellectual disabilities, developmental delays, or multiple congenital anomalies.5 We particularly recommend CentoGenome for patients in the following cases:
The symptoms are very broad, complex, or unspecific, not pointing towards specific disease or typical phenotype, as:
- Clinical or genetic heterogeneity (e.g., intellectual disability/developmental delay, epilepsy, muscular dystrophies/muscular disorders, ataxia, neuropathies, cardiomyopathies, skeletal dysplasias, immunodeficiency, deafness, blindness)
- Diseases or patients with atypical clinical presentations or phenotypes (e.g., newborn with congenital heart defects and idiopathic thrombocytopenic purpura associated with the KMT2D gene, indicative of Kabuki syndrome type)
- Patients with 'blended' clinical presentations and clinical suspicion of dual diagnosis (e.g., patient with deafness and ichthyosis, intellectual disability, and severe immunodeficiency)
- Suspicion of a microdeletion or microduplication syndrome (e.g., patients with neurodevelopmental delay, multiple dysmorphisms and/or malformations, growth delay)
- Suspicion of a mitochondrial disorder (e.g., patient with muscular weakness, cardiomyopathy, visual problems)
Prior testing did not provide a conclusive diagnosis, like:
- Patient with autosomal dominant spastic paraplegia, but a negative result for the gene panel
- Patient with neurodevelopmental delay and similarly affected siblings, but a negative testing with microarrays and WES
- Any case where a genetic disorder is suspected but WES is negative
A fast diagnosis is a medical necessity and there is not always the time for serial testing strategies, as seen with:
- Patients severely ill for whom a diagnosis may direct or alter medical management (e.g., children with seizures, hypotonia, neurological abnormalities, and a rapidly deteriorating clinical status)
- Newborns, babies and children where a rapid diagnosis is crucial for prognosis and treatment decisions (e.g., critically ill newborns and children in the neonatal and pediatric intensive care, NICU and PICU)
In one of our WGS studies, where WGS was performed in a clinical setting in one of the largest patient cohorts to date, we demonstrate the diagnostic strength of WGS as the most comprehensive genetic test and its strengths compared to WES.7 The results also support that WGS should be considered the 'standard of care' for genetic testing, as well as a first-line stand-alone test for rare disease patients.
CentoGenome covers a broad spectrum of disorders encompassing >7,000 rare diseases, helping you tackle challenging and undiagnosed patient cases across all stages of life.
Tailored Testing and Life-Long Diagnostic Support
We offer flexible testing options and additional services to provide solutions tailored to the needs of your patients. Our services include offerings such as Whole Genome Sequencing (WGS) for ongoing pregnancies with fetal abnormalities (CentoGenome Prenatal), as well as cutting-edge multiomic WGS solutions (CentoGenome MOx 1.0 and 2.0) integrating different data sets to capture the most complete clinical picture. For more details, please see the table below.
When a rapid diagnosis is a medical necessity
A rapid diagnosis can be critical for timely and appropriate medical intervention. Several recent studies demonstrate how the high diagnostic yield and short turnaround time of WGS enables improved clinical decision making in critically ill newborn infants and children in the NICU and PICU.8–12 CentoGenome, with a turnaround time as fast as 15 days or less, acts as a comprehensive and accurate tool that will potentially improve critical decision making when used as a first-line test for diagnosing critically ill newborns or children.
Committed to improving the lives of patients
We offer flexible testing options and additional services tailored to your patient’s needs, paired with life-long diagnostic support via a free-of-charge reclassification program, as well as an affordable case-level reanalysis.
Options & Additional Services | |||
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| Testing Design* |
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| Testing Solutions | CentoGenome |
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| CentoGenome MOx** |
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| CentoGenome Prenatal*** |
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| CentoGenome POC*** |
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| CentoGenome Variants |
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| Additional Options | FAST Processing | ≤ 15 business days (not applicable with CentoGenome MOx 2.0) | |
| Free of Charge Raw Data |
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| Life-Long Diagnostic Support**** |
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TAT: Turnaround time
* Solo: only the affected index patient is tested; Duo: index patient and affected or unaffected family member are tested; Trio: index patient and two family members, affected or unaffected, are tested; PLUS: additional family member beyond Trio is tested
** More details about our Multiomic Solutions.
*** WGS-based mitochondrial genome analysis and screening for UPD, repeat expansions, SMN1/SMN2 CNVs and GBA1 gene conversion is not offered due to technical limitations. More details about Prenatal Testing.
**** Case reanalysis is available only for orders with original sequencing data from August 2020 onwards. More details about Variant Reclassification Program.
Best-in-Class Medical Reporting and Advanced Insights
Pinpointing the disease-causing variants among millions is challenging. NEW CentoGenome leverages our experience in analyzing tens of thousands of genomes/exomes from patients worldwide to help you diagnose patient with suspicion of genetically linked disorders.
When choosing our WGS services, physicians, patients, and partners can trust that they will receive high-quality sequencing, utilizing state-of-the-art WGS PCR-free technology, combined with advanced data analysis through our fully automated CE-IVD bioinformatics pipeline. Following this, our team of highly trained clinical geneticists and scientists meticulously interpret the data, cross-checking every medical report. We conduct internal confirmatory testing free-of-charge using orthogonal methods when necessary and utilize the CENTOGENE Biodatabank to confirm results and validate variant pathogenicity, ensuring the delivery of best-in-class medical reports.
Test reports always contain clear actionable clinical results, recommendations, and follow-up options. They are phenotype-driven and focused on reporting findings related to the patient’s clinical presentation/patient’s indications.
Additional Information & Resources
CentoGenome Product Sheet
Whole Genome Sequencing
CentoGenome Trio – Index, Fragile X Syndrome, with Positive Secondary and Carriership Findings
POSITIVE RESULT, pathogenic variants identified, secondary finding identified
CentoGenome Trio – Mother, Carrier Status Confirmed, with Negative Secondary Findings
CARRIER STATUS CONFIRMED, pathogenic variant identified
CentoGenome Trio – Father, Negative Result, with Positive Secondary Findings
NEGATIVE RESULT, secondary finding identified
NEW CentoXome® – Turning Our Expertise Into Your Advantage
Dr. Aida Bertoli-Avella and Dr. Jorge Pinto-Pasto provide you with an exclusive look into our enhanced Whole Exome Sequencing (WES) solution – NEW CentoXome.
NEW CentoXome – Turning Years Into Days
Throughout the CentoTalk, Maximilian Schmid, M.D., and Jorge Pinto Basto, M.D., will provide a detailed overview of CENTOGENE’s new and enhanced Whole Exome Sequencing (WES) solution.
Multiomics and Biomarkers in Rare Diseases Supporting Development and Commercialization of Orphan Drugs
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References
1Data on file at CENTOGENE; 2Boycott et al. 2015, PMID: 25951830; 3Chinese Medical Doctor Association Medical Genetics Branch 2019, PMID: 31216797; 4Manickam et al. 2021, PMID: 34211152; 5Sachdev et al. 2021., PMID: 33566436; 6Souche et al. 2022, PMID: 35577938; 7Bertoli-Avella et al. 2020, PMID: 32860008; 8Kingsmore et al. 2019, PMID: 31564432; 9Petrikin et al. 2018, PMID: 29449963; 10Soden et al. 2014; PMID: 25473036; 11Van Diemen et al. 2017, PMID: 28939701; 12Willig et al. 2015, PMID: 25937001; 13Clinical Genome Resource. https://www.clinicalgenome.org/ ; 14Miller et al. 2021, PMID: 34012069; 15Richards et al. 2015, PMID: 25741868