CeGaT Brings New Dimension to Exome Diagnostics

CeGaT aims to solve all genetically-caused cases of disease to help physicians state a diagnosis. To pursue this goal, CeGaT incorporated its long-term expertise and latest scientific knowledge in an innovative diagnostic tool: CeGaT Exome Xtra is the most powerful genetic diagnostic option for patients with complex, unspecific, and rare diseases.

CeGaT has been utilizing the power of genetic diagnostics for more than a decade as it introduced gene panels to clinical genetic diagnostics in 2010. Since then, the company has been continuously updating the panels using the newest literature and in close collaboration with clinical experts. Based on all the knowledge gained, CeGaT Exome Xtra is the latest innovation in genetic diagnostics, particularly suitable for solving the most complex patient cases.

With CeGaT Exome Xtra, patients and their treating physicians benefit from a unique approach that combines the advantages of whole-exome sequencing (WES) and whole-genome sequencing (WGS), while avoiding their disadvantages. It outperforms commercially available WES and WGS and increases diagnostic yield.

CeGaT Exome Xtra – Better than exome, smarter than genome

CeGaT Exome Xtra binds all accomplishments of genetics in one single test.

  • Extra smart clinical design

CeGaT Exome Xtra considers all medically-relevant regions throughout the complete genome, while standard WES only comprises the coding regions. All known pathogenic and likely pathogenic intronic variants are included, as well as disease-associated individual transcripts and cryptic exons. Regular updates ensure that it always corresponds to the latest science and thus provides the ideal basis for genetic diagnostics.

  • Extra thorough analysis

CeGaT’s data analysis goes beyond regular exome diagnostics as it accounts for variants in genes with reduced penetrance, variable expressivity, and imprinting effects. It furthermore assesses copy number variants (CNVs), also including combinations of sequence variants (SNVs, InDels) with CNVs. All family constellations (duo, trio, etc.) can be analyzed.

  • Extra insightful results

A total of four scientific experts and medical doctors contributes to every medical report – generating the best possible results with maximum medical usability.

CeGaT Exome Xtra outperforms WGS in a diagnostic setting.

Although WGS is sometimes described as the most comprehensive genetic analysis possible, its coverage is often too low for reliable variant detection, and mosaicism cannot be detected. CeGaT Exome Xtra covers more relevant regions at higher coverage and thereby delivers higher sensitivity – at much lower costs than WGS. At the same time, thousands of irrelevant variants usually obtained by WGS analyses are avoided, improving diagnostic speed and accuracy. A detailed comparison can be found in our Tech Note „The Best Possible Exome“.

Whole-genome sequencing is a great tool for research. Until it is ready for diagnostic use, CeGaT Exome Xtra provides the clinical genome diagnostics to help patients today.

All exome analyses include the regular re-evaluation variants of uncertain clinical significance (VUS) for two years to further incresase the diagnostic yield. This service is free of charge.

Further information on CeGaT Exome Xtra can be found here. For any question, please contact us at sales@cegat.com.

New Service: CeGaT’s Diagnostic Panel “Fertility” Identifies Genetic Causes for Infertility

CeGaT’s genetic infertility testing aims to identify the cause of involuntary childlessness: An appropriate diagnosis provides clarity for those affected. Based on the findings, the attending physicians can further improve the chances of having a child.

People that have been trying in vain to start a family for a long time experience enormous psychological pressure, emotional suffering, and financial burden. It is, therefore, crucial for their quality of life to identify the cause as soon as possible.

According to estimates, up to 10 percent of involuntary childlessness stems from genetic causes, such as hereditary hormonal disturbances. CeGaT now offers one of the most comprehensive genetic diagnostic panels for female and male infertility. It comprises all relevant genes known according to the current state of science. The 141 genes in men and women are divided into 11 gene sets covering the most frequent conditions that cause genetic infertility or recurrent pregnancy loss:

  • Primary ovarian insufficiency (FER01)
  • Premature ovarian failure (FER02)
  • Ovarian dysgenesis (FER03)
  • Recurrent pregnancy loss, early embryonic arrest, and thrombophilia (FER04)
  • Thyroid dyshormogenesis and congenital hypothyroidism (FER05)
  • Azoospermia (FER06)
  • Oligozoospermia (FER07)
  • Oligoastheno-teratozoospermia (FER08)
  • Irregularly sperm and flagella morphology (FER09)
  • Hypogonadotropic hypogonadism with or without anosmia (FER10)
  • Pituitary hormone deficiency (FER11)

Once treating physicians know the genetic cause, they can determine the optimal procedure to hopefully realize their patients’ desire for a child, such as tailored hormonal therapies or assisted reproductive technologies. Futile attempts can be avoided.

CeGaT’s diagnostic panel “Fertility” is also relevant for families in which genetic infertility has been diagnosed. Relatives who wish to have children can have their genetic predisposition tested before they try to start a family. Further information on the service can be found here.

All diagnostic panels include a panel-wide deletion/duplication screening using the copy number variation (CNV) track. We validate our analysis using MLPA or qPCR. The del/dup analysis contributes to CeGaT’s high-quality medical reports and provides you with all major analysis options available.

CeGaT Introduces Regular Re-evaluation of Variants of Uncertain Significance (VUS)

CeGaT’s VUS re-evaluation reassesses previously reported variants of uncertain clinical significance (VUS) as soon as new scientific evidence on the pathogenicity of the variant is available. This leads to an even higher number of diagnoses made by CeGaT.

Variants of uncertain clinical significance (VUS) are one of the five classes defined by the American College of Medical Genetics and Genomics (ACMG) for the interpretation of genetic variants. A variant is classified as VUS if, at the time of examination, it cannot be determined whether it is pathogenic or benign.

Genetic research is making great progress and is constantly improving our knowledge of disease-causing variants. This makes it likely that, over time, a VUS will be better understood and classified as pathogenic (“probably pathogenic” / “pathogenic”) or benign (“probably benign” / “benign”).

In the event of such a VUS re-evaluation, CeGaT proactively informs the treating physicians. In addition, the re-evaluated variant is interpreted by our specialists with reference to the clinical picture of the patient and a revised medical report is issued.

The re-evaluation is very relevant for the care and treatment of patients and family members. CeGaT’s VUS reclassification is available from now on. The service is free of charge and is offered for 5 years from the date of the initial medical report. Further information on the service can be found here. If you have any questions, please do not hesitate to contact our team at sales@cegat.de.

Update of the Molecular Pathology Panel for Cancer Diagnostics

CeGaT GmbH has expanded its molecular pathology panel and is now able to detect additional therapy-relevant gene mutations in tumors. The diagnostic panel allows a rapid and cost-efficient examination of the most common tumor entities.

The Molecular Pathology Panel has been significantly revised, following the latest scientific findings and our own insights from cancer diagnostics. 17 additional genes and newly created gene sets expand the panel’s range of applications. It is used for the focused analysis of therapy-relevant genes and their alterations in the most common cancers. These genes are highly relevant for a comprehensive understanding and a clear description of the clinical picture. This knowledge serves as the basis for recommending the appropriate treatment as there are specific therapy options for the selected genes and tumor entities.

After the panel update, CeGaT covers three additional tumor diseases with new gene sets. These are

  • Medullary thyroid carcinomas (PAT07)
  • Myelodysplastic syndromes (PAT08)
  • Cholangiocellular carcinomas (PAT09)

The gene set for breast, ovarian, and pancreatic carcinoma (PAT06) has been split up for more precise diagnostics: Pancreatic carcinomas are now examined through a separate gene set (PAT10).

Due to the high therapeutic relevance of PARP inhibitors in BRCA-mutated breast and ovarian cancers, CeGaT now also offers a separate BRCA1/2 test (PAT11). The BRCA1/2 test can also be requested by physicians as part of predictive genetic diagnostics.

As a further change, the gene sets for melanomas (PAT01), colon carcinomas and gastric carcinomas (PAT02), and lung carcinomas (PAT03) have been supplemented with additional genes. The new version of the panel also allows the analysis of the genes NTRK1, FGFR1, FGFR2, FGFR3, BRAF, ALK, RET and ROS1 to detect therapy-relevant translocations. Due to their high therapeutic value, they are always included routinely for the gene sets PAT01 to PAT10.

For further information regarding the panels, please do not hesitate to contact us at sales@cegat.de. The new panel can be requested here.

Panel Update: Improvement of the Panels for Epilepsy, Metabolic Diseases & Brain Development Disorders and Mitochondriopathies

The diagnostic panels for the disease categories Epilepsy, Metabolic Diseases & Brain Development Disorders (EPI) and Mitochondriopathies (MIT) have been updated in accordance with the latest scientific findings.

As part of the update, the gene sets for metabolic diseases (MET) have been integrated into the Panel for Mitochondriopathies (MIT). This new, fourth version of the Panel for Metabolic Diseases including Mitochondriopathies now comprises 539 genes, divided into 14 gene sets for metabolic diseases and 9 for mitochondriopathies. The reorganization treats mitochondriopathies as part of metabolic diseases. A grouping of disease patterns was thereby created that offers the treating physician new differential diagnosis options.

Since the majority of the MET gene sets have been moved, the EPI panel has been renamed to Panel for Epilepsy & Brain Development Disorders. It now contains 7 gene sets for epilepsy and 11 for brain development disorders. Still part of the panel are the phenotypes for metabolic diseases that offer differential diagnosis options: congenital glycosylation disorders (MET01), lysosomal diseases (MET02), and peroxisomal biogenesis defects (MET03). In total, the panel now comprises 699 genes in 21 gene sets.

The following changes have been made to individual gene sets of the two panels:

  • The gene set for epilepsy & developmental delay (incl. epileptic encephalopathies) (EPI02) has been extended by 18 genes.
  • GPI anchor deficiencies / hyperphosphatasia (EPI12) has been supplemented by 5 genes.
  • The number of analyzed genes for macrocephaly (BRN04) has been increased by 10.
  • The gene set for Joubert’s syndrome (BRN07) can now be ordered as an integral part of the EPI panel.
  • The gene set for Leukodystrophies and differential diagnoses (BRN10) now contains 51 additional genes.
  • A new gene set is available for the diagnosis of the Kabuki syndrome (BRN11).

Please also note our cost and time efficient large panel approach. We always sequence all 699 (EPI) respectively 539 (MIT) genes of the panel and analyze the ordered gene set. As a result, we can quickly expand the analysis to other gene sets. Furthermore, we offer to check all genes of the panel for ACMG class 4 and 5 variants. All our diagnostic panels include a panel-wide deletion/duplication analysis – free of charge. We validate pathogenic deletions or duplications by means of MLPA or qPCR before we report them. The highest quality possible is our standard for diagnostics.

For further information on the panels, please contact us at sales@cegat.de for advice. The new panels can be requested here (EPI) and here (MIT).