Scientific Publications

Modifiers of Genetic Disease

Therapeutic strategies for monogenic diseases may be derived from the identification and understanding of disease-modifying factors. Researchers at CENTOGENE have been applying this rather novel approach, including in collaborative settings with academic colleagues from institutions around the world.

Therapeutic strategies for monogenic diseases may be derived from the identification and understanding of disease-modifying factors. Researchers at CENTOGENE have been applying this rather novel approach, including in collaborative settings with academic colleagues from institutions around the world. A proof-of-concept study resulting from one such collaboration has now been published in Nature Communications.

A Novel Genetic Cause for Autoinflammation

A global consortium, of which CENTOGENE was a part of, recently identified a novel autoinflammatory disorder that primarily affects the nervous system. The study was published in the American Journal of Human Genetics.

Genetic inflammatory disorders are quite rare, particularly those presenting with a pathological increase, rather than decrease, of inflammatory activity. A global consortium, of which CENTOGENE was a part of, recently identified a novel autoinflammatory disorder that primarily affects the nervous system. The study was published in the American Journal of Human Genetics.

Globally Rare – Locally Common

A corresponding study focusing on leukodystrophies in Saudi Arabia was recently published in Frontiers in Pediatrics.

Genetic diseases that are generally rare may still have a high prevalence in certain geographic regions. As a major diagnostic partner for physicians in certain countries, CENTOGENE has been able to systematically investigate patient cases based on highly uniform data sets. A corresponding study focusing on leukodystrophies in Saudi Arabia was recently published in Frontiers in Pediatrics.

One Gene – Two Modes of Inheritance

While most genetic disorders have one clearly defined mode of inheritance, the existence of rare exceptions is being increasingly recognized. A recent diagnostic finding at CENTOGENE revealed that mutations in PRKD1 can cause heart defects not only in an autosomal dominant, but also in an autosomal recessive manner. The findings were published in the journal Genes.

Leveraging the CENTOGENE Biodatabank and Genomic Testing to Discovers Six New Rare Diseases

By performing deep genetic analyses and Bio/Databank mining, CENTOGENE discovered six novel gene-disease associations and evidence supporting 31 candidate genes – ultimately diagnosing over 90 patients. The findings were published in the prestigious journal Genetics in Medicine.

While technology has advanced over the past ten years, more than half of patients with genetic diseases remain undiagnosed, even after applying genome-wide diagnostic approaches. By performing deep genetic analyses and Bio/Databank mining, CENTOGENE discovered six novel gene-disease associations and evidence supporting 31 candidate genes – ultimately diagnosing over 90 patients. The findings were published in the prestigious journal Genetics in Medicine.

Recognition of CENTOGENE’s Scientific Expertise

Review articles constitute a unique type of scientific publication, as they summarize, rather than present, observations and interpretations. In prestigious journals, they are commonly provided by the most recognized experts in the field. A pertinent example involving CENTOGENE authorship was recently published in the Journal of Neural Transmission.

A Genetic Cause for Infectious Disease

While infectious diseases are commonly connected to environmental factors, genetic defects in some genes can strongly increase a person’s susceptibility to infections. Data generated at CENTOGENE helped to identify yet another example of this rare phenomenon. The findings, which revealed a novel disorder of the immune system, were published in the Proceedings of the National Academy of Sciences of the United States of America.

The Importance of Neuronal Membrane Biology

Nerve cells have a uniquely large surface-to-volume ratio, suggesting a central role for proper membrane turnover in these cells. A recent study confirmed this paradigm by showing that a membrane fusion protein is mutated in patients with a novel form of ataxia. These findings, which critically relied on genetic insights provided by CENTOGENE, were published in BRAIN, one of the leading neurological journals.

A Dispute on Rare Disease Diagnostic Offerings

CENTOGENE was amongst the first providers of diagnostic Whole Genome Sequencing (WGS) and published real-life experience with this technology in 2020. That paper was subsequently challenged in a ‘Letter to the Editor’ by a competitor. We happily accepted the offer to draft a reply – advocating our arguments in favor of WGS and emphasizing our ambition to offer the best available diagnostic solutions to our patients. The dispute appeared in the European Journal of Human Genetics.

CENTOGENE was amongst the first providers of diagnostic Whole Genome Sequencing (WGS) and published real-life experience with this technology in 2020. That paper was subsequently challenged in a ‘Letter to the Editor’ by a competitor. We happily accepted the offer to draft a reply – advocating our arguments in favor of WGS and emphasizing our ambition to offer the best available diagnostic solutions to our patients. The dispute appeared in the European Journal of Human Genetics.

An Unusual Kind of Repeat Expansion Disorder

Repeat expansions are the cause of Huntington’s disease and several forms of ataxia. The affected repeat units are usually three to six nucleotides in length, and pathogenic alleles have accumulated at least several dozen units. In a newly described neurological disorder, a single extra unit of a 10-nucleotide repeat is sufficient to cause disease. The study in which CENTOGENE contributed significant insights was published in the highly prestigious journal Brain.

Repeat expansions are the cause of Huntington’s disease and several forms of ataxia. The affected repeat units are usually three to six nucleotides in length, and pathogenic alleles have accumulated at least several dozen units. In a newly described neurological disorder, a single extra unit of a 10-nucleotide repeat is sufficient to cause disease. The study in which CENTOGENE contributed significant insights was published in the highly prestigious journal Brain.

Diagnostic Relevance of Intronic Variants

Proper splicing of mRNA requires certain DNA sequence motifs. Since these motifs are very diverse, the effects of variants in them are not easy to predict. By combining CENTOGENE’s genetic testing with the histology of patient samples, an unusual intronic variant was recently revealed to be clearly pathogenic by disrupting a splice donor motif. The findings were published in Molecular Genetics & Genomic Medicine.

Proper splicing of mRNA requires certain DNA sequence motifs. Since these motifs are very diverse, the effects of variants in them are not easy to predict. By combining CENTOGENE’s genetic testing with the histology of patient samples, an unusual intronic variant was recently revealed to be clearly pathogenic by disrupting a splice donor motif. The findings were published in Molecular Genetics & Genomic Medicine.

Exemplifying the Strengths of Genome Sequencing

Certain genetic variants are easily missed by Exome Sequencing (ES), but readily detected by Genome Sequencing (GS). Utilizing the superiority of the latter technology, CENTOGENE identified such a variant as the cause of a novel disorder. Teaming up with academic colleagues for functional studies on this finding resulted in a high impact publication in Genetics in Medicine, with shared senior authorship for CENTOGENE as a reflection of the company’s significant role in the study.

Certain genetic variants are easily missed by Exome Sequencing (ES), but readily detected by Genome Sequencing (GS). Utilizing the superiority of the latter technology, CENTOGENE identified such a variant as the cause of a novel disorder. Teaming up with academic colleagues for functional studies on this finding resulted in a high impact publication in Genetics in Medicine, with shared senior authorship for CENTOGENE as a reflection of the company’s significant role in the study.

Utilization of CentoMD® in Scientific Settings

The interpretation of newly observed genetic variants that are suspected to cause disease requires knowledge about their occurrence in different populations. CENTOGENE’s uniquely rich and diverse database – CentoMD® – is frequently encountered by academic consortia in need of such information. A recent example of this type of collaboration with the scientific community enabled the discovery of a new cause of inherited deafness. The findings were published in Human Genetics.

The interpretation of newly observed genetic variants that are suspected to cause disease requires knowledge about their occurrence in different populations. CENTOGENE’s uniquely rich and diverse database – CentoMD® – is frequently encountered by academic consortia in need of such information. A recent example of this type of collaboration with the scientific community enabled the discovery of a new cause of inherited deafness. The findings were published in Human Genetics.

Turning Rare Disease Networks into Knowledge

CENTOGENE’s well-recognized expertise in Gaucher disease (GD) has helped to establish a global network of physicians interested in and aware of this rare metabolic disorder. The fact that CENTOGENE is meanwhile the primary nationwide GD partner in many countries enables unprecedented insights into local prevalence, genotypes, and phenotypes. As an example, CENTOGENE recently described the Albanian GD population in the Journal of Inherited Metabolic Diseases Reports.

CENTOGENE’s well-recognized expertise in Gaucher disease (GD) has helped to establish a global network of physicians interested in and aware of this rare metabolic disorder. The fact that CENTOGENE is meanwhile the primary nationwide GD partner in many countries enables unprecedented insights into local prevalence, genotypes, and phenotypes. As an example, CENTOGENE recently described the Albanian GD population in the Journal of Inherited Metabolic Diseases Reports.

Genetic Cause of Impaired Neurodevelopment

Development of the nervous system is a complex process, with NEUROG1 being one out of many genes involved. The critical role of this gene was recently confirmed by CENTOGENE, when a patient with disturbed neurodevelopment was observed as having the gene knocked out. The finding was published in Clinical Genetics.

Development of the nervous system is a complex process, with NEUROG1 being one out of many genes involved. The critical role of this gene was recently confirmed by CENTOGENE, when a patient with disturbed neurodevelopment was observed as having the gene knocked out. The finding was published in Clinical Genetics.