Update of the Diagnostic Panel for Neuromuscular Diseases

As part of the regular diagnostic panel updates, CeGaT has updated and expanded the Panel for Neuromuscular Diseases (NMD) following the latest scientific data. 33 genes have been added: They increase the probability of identifying the causative variant and cover additional clinical pictures.

One of the new genes added is the sorbitol dehydrogenase gene (SORD). In the recent publication by Cortese and colleagues1, it was shown that variants in this gene are the most common identified cause of autosomal recessive inherited neuropathy. Therefore, the inclusion of SORD in the panel allows making significantly more diagnoses, which goes along with new therapeutic possibilities for the treating physicians

After the update, the panel’s gene set for arthrogryposis  (NMD14) contains 14 additional genes and now also covers the two clinical pictures of fetal akinesia and congenital contracture syndromes. Arthrogryposis is the term used to describe the symptoms of congenital joint contractures in at least two regions of the body that occur in a variety of often severe clinical pictures.

All CeGaT panels are examined with CeGaT’s large panel approach. We always sequence all genes of a panel and evaluate the requested gene set. If necessary, we can quickly extend the evaluation to other gene sets. This gives you access to flexible and cost-efficient differential diagnostics. In addition, we offer a screening of all differential diagnostic relevant genes of the panel for variants of ACMG classes 4 and 5. CeGaT’s panel diagnostics also include the free of charge regular re-evaluation of variants of uncertain clinical significance (VUS) to increase the diagnostic yield further.

We are convinced that all patients should receive the best possible diagnostics. For this reason, our panels routinely examine single nucleotide variation (SNVs) and copy number variants (CNVs) and check for mosaicism. If necessary, we validate pathogenic deletions or duplications using MLPA or qPCR before reporting. The highest quality is our standard.

For further information on the panel, please contact us at sales@cegat.com. The new panel can be ordered here.

1 Cortese, A., Zhu, Y., Rebelo, A.P. et al. Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Nat Genet 52, 473–481 (2020). https://doi.org/10.1038/s41588-020-0615-4

Update of the Panel for Hereditary Tumor Diseases (CAN)

Prevention is the most important measure in the fight against tumor diseases. Every fifth tumor develops due to a hereditary predisposition. Knowing predispositions and being able to initiate appropriate early detection examinations is a central component in the prevention of metastatic and late-detected disease progression.

Since its foundation in 2009, CeGaT has been specializing in comprehensive large panel diagnostics. We pursue a panel-based approach in the field of tumor diagnostics, as it allows us to achieve the highest possible sensitivity and thus the highest possible certainty in the clarification of hereditary predispositions to tumor diseases.  We always sequence all genes of the tumor panel in parallel and evaluate the requested gene set according to the indication with priority. Hereditary breast and ovarian cancer, hereditary colorectal cancer, hereditary pancreatic cancer, and hereditary prostate cancer are among the most frequently requested indications. However, rare tumor diseases such as brain tumors, skin tumors, or endocrine tumors can also be hereditary.

Based on scientific findings relevant to patients, CeGaT has now again expanded and technically optimized its tumor diagnostics in the context of the regular product updates.  New gene sets have been included in the large Panel for Hereditary Tumor Diseases (CAN). Our current update thus expands the panel’s range of application in germline diagnostics, which allow the reliable and fast detection of genetic cancer predispositions.

Six new tumor entities in addition to the already examined indications are now covered by the panel:

– Gastrointestinal stromal tumors (CAN15)

– Gastrointestinal neuroendocrine neoplasia (CAN16)

– Thyroid neoplasias (CAN17)

– Lung tumors (CAN18)

– Urinary tract tumors (CAN19)

– Basal cell carcinomas (CAN20)

The detection of pathogenic and thus possibly disease-causing variants in the genes examined is just as relevant for the early detection and therapy of those affected as it is for predictive diagnostics in healthy family members.

Our diagnostic services give you access to the most comprehensive, flexible, and cost-efficient differential diagnostics with the highest possible diagnostic sensitivity performed by a nationally (by DAkkS) and internationally (by CAP/CLIA) accredited laboratory. If required, we can quickly extend the analysis to other gene sets at any time after individual consultation. Also, we offer an “all-inclusive” screening of all differential diagnostic relevant genes of the panel for variants of ACMG classes 4 and 5 if an indication in a family cannot be assigned to one gene set. CeGaT’s diagnostic services also include the regular re-evaluation of variants of uncertain clinical significance (VUS). This service is available free of charge and can be requested at any time, to ensure that the families are cared for throughout the disease and to increase the rate of diagnostic clarification further. Germline diagnostics considers single nucleotide variants (single-nucleotide variants, SNVs), small insertions and deletions (INDELs), and copy number variants (CNVs) of single and/or multiple exons. For each gene included in the gene sets, we analyze all coding regions as well as known pathogenic intronic variants.

In the case of variants of uncertain clinical significance, we also recommend somatic tumor diagnostics examining tumor tissue of affected family members. Please feel free to contact us at any time if you have any questions. We are at your disposal at sales@cegat.com. The new panel can be requested here.

Update of the Panels for Blood Disorders and Immune Disorders

CeGaT has updated its Panels for Blood Disorders (BLD) and Immune Disorders (PID) according to the latest state of scientific knowledge. The diagnostic sensitivity increased even further. As part of the updates, the composition and structure of the panels have been revised to more clearly differentiate the disease patterns covered. This provides physicians with optimized differential diagnostics for their patients.

Update of the Panel for Blood Disorders (BLD)

In the Panel for Blood Disorders (BLD), the gene set for thrombocytopenia (BLD-02) has been divided into:

  • Bleeding disorders: coagulopathies, hemophilia and (macro-) thrombocytopenias (BLD-03)
  • Bleeding disorders with thrombophilia and thrombocythemia (BLD-04)

This division has created new differential diagnostic options. The now six instead of five gene sets of the panel were renumbered accordingly.

Update of the Panel for Immune Disorders (PID)

Additional gene sets have been included in the Panel for Immune Disorders. The other gene sets have been optimized in this course: The panel is now divided into autoinflammatory syndromes respectively autoimmune diseases (AID) and primary immunodeficiencies (PID). This new structuring helps to differentiate phenotypes better and to determine the most appropriate diagnostics.

Autoinflammatory syndromes and autoimmune diseases (AID)

The gene sets for autoinflammatory syndromes and autoimmune diseases cover diseases in which the body’s immune system is malfunctioning – it initiates immune responses against parts of the own body or a dysregulated inflammatory response. Thanks to new gene sets, the panel now additionally covers the following diseases:

  • Defects of regulatory T cells and IPEX-like phenocopies
  • Inflammation with symptoms in connective and supporting tissue
  • Type I interferonopathies and differential diagnoses
  • Immune dysregulation in the context of syndromal clinical pictures

Immunodeficiencies (PID)

The gene sets on primary immunodeficiencies examines immune deficiencies that can lead to increased susceptibility to infections of differing severity. The 16 gene sets of the panel can detect diseases such as:

  • Primary antibody deficiencies
  • Severe combined immunodeficiency (SCID), also in the context of NG screening
  • Hyper-IgE syndrome and differential diagnoses
  • Adaptive immunodeficiency in syndromes
  • Proneness to infection: Mycobacterial Infections
  • Proneness to infection: Viral Infections
  • Generalized verrucosis
  • Defects in signaling pathways that are important for immune responses

Panel Updates in Cooperation with Partners

The panel updates have been developed together with cooperation partners at the University Hospitals of Freiburg, Düsseldorf, and the Helios Klinikum Krefeld. Prof. Dr. med. Stefan Ehl continues to assist us in the management of ALPS and general AID cases, Prof. Dr. med. Klaus Warnatz supports us in CVID and B-cell deficiency cases.

All CeGaT panels are examined with CeGaT’s large panel approach. We always sequence all genes of a panel and evaluate the requested gene set. If necessary, we can quickly extend the evaluation to other gene sets. This gives you access to flexible and cost-efficient differential diagnostics. In addition, we offer a screening of all differential diagnostic relevant genes of the panel for variants of ACMG classes 4 and 5. CeGaT’s panel diagnostics also include the free of charge regular re-evaluation of variants of uncertain clinical significance (VUS) to increase the diagnostic yield further.

We are convinced that all patients should receive the best possible diagnostics. For this reason, our panels routinely examine single nucleotide variation (SNVs) and copy number variants (CNVs) and check for mosaicism. If necessary, we validate pathogenic deletions or duplications using MLPA or qPCR before reporting. The highest quality is our standard.

For further information on the panels, please contact us at sales@cegat.com. The new panels can be ordered here (BLD) and here (PID).

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.

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.