Scientific Publications

Fetal exome sequencing in a real world setting

Fetal exome sequencing (fES) has been available for some time, but systematic analyses of the outcome are scarce.

Fetal exome sequencing (fES) has been available for some time, but systematic analyses of the outcome are scarce. Based on a series of cases evaluated at CENTOGENE, diagnostic yield of fES was found to be impacted by (i) presence of ultra-sound abnormalities, (ii) positive family history, and (iii) involvement of certain organs. The study was published in the online journal Frontiers in Genetics.

Insights into the pathophysiology of Niemann-Pick disease 

Lysosomal storage disorders (LSDs) are a central focus of research as performed at CENTOGENE.

Lysosomal storage disorders (LSDs) are a central focus of research as performed at CENTOGENE. Characterization of a mouse model for the LSD Niemann-Pick disease suggested that defects in a cholesterol-associated signaling pathway may contribute to the neurological manifestations of this disorder. The study was published in the journal Cerebral Cortex.

Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test

Interpretation of genetic variants as pathogenic or benign strongly benefits from functional investigations. Researchers at CENTOGENE, together with colleagues from Rostock University, have developed a pertinent cellular assay for the NPC1 gene, involved in Niemann-Pick disease. The successful application of this assay was recently published in International Journal of Molecular Sciences.

Interpretation of genetic variants as pathogenic or benign strongly benefits from functional investigations. Researchers at CENTOGENE, together with colleagues from Rostock University, have developed a pertinent cellular assay for the NPC1 gene, involved in Niemann-Pick disease. The successful application of this assay was recently published in International Journal of Molecular Sciences.

Unprecedented insights into an ultra-rare disorder

CENTOGENE’s strategy to provide accurate genetic diagnoses incorporates standardized compilation and curation of clinical observations. Its sample collection platform CentoCard®, in addition, facilitates biochemical analysis in a research setting for consented cases. The resulting datasets are highly unique as they enable a conceptual connection of genotypic, phenotypic and biomarker levels. The success of this approach was demonstrated by using the ultra-rare Hyaline Fibromatosis Syndrome as an example.

CENTOGENE’s strategy to provide accurate genetic diagnoses incorporates standardized compilation and curation of clinical observations. Its sample collection platform CentoCard®, in addition, facilitates biochemical analysis in a research setting for consented cases. The resulting datasets are highly unique as they enable a conceptual connection of genotypic, phenotypic and biomarker levels. The success of this approach was demonstrated by using the ultra-rare Hyaline Fibromatosis Syndrome as an example.

Genetic modifiers in hereditary breast cancer

Age at manifestation varies widely in carriers of cancer susceptibility variants. A recent study involving scientists from CENTOGENE suggested that this phenomenon is partially explained by certain genetic modifiers. The study appeared in BMC Cancer in August.

Delineation of a novel neuro-metabolic syndrome

Neurodevelopmental defects are genetically very diverse, and novel corresponding disease genes continue to be discovered. A recent example is the association between PIGB inactivation and a congenital neuro-metabolic syndrome. The study, which partially built on analyses performed at CENTOGENE, was published in the August issue of American Journal of Human Genetics.

Novel neurodevelopmental disorder identified

Numerous genes are important for proper development of the nervous system. As part of an international research team, researchers at CENTOGENE contributed to the identification of a novel cause for impaired neurodevelopment.

Numerous genes are important for proper development of the nervous system. As part of an international research team, researchers at CENTOGENE contributed to the identification of a novel cause for impaired neurodevelopment. They identified mutations in SVBP, the protein product of which is responsible for maintaining microtubule plasticity. These findings were published in Human Molecular Genetics.

Editorial on biomarkers

In a corresponding Editorial for the newly launched Journal of Biochemical and Clinical Genetics, CEO Prof. Arndt Rolfs and CSO Prof. Peter Bauer discuss the utility of biomarkers in the field of rare diseases.

The reputation of CENTOGENE’s scientists is reflected by membership in several editorial boards. In a corresponding Editorial for the newly launched Journal of Biochemical and Clinical Genetics, CEO Prof. Arndt Rolfs and CSO Prof. Peter Bauer discuss the utility of biomarkers in the field of rare diseases.

Improved diagnostic options

Large genomic rearrangement mutations are hard to detect by conventional genetic diagnostic approaches, but easily identified by the MLPA technology.

Large genomic rearrangement mutations are hard to detect by conventional genetic diagnostic approaches, but easily identified by the MLPA technology. For MPS I, a recessive lysosomal storage disorder, a correspondingly developed approach involving scientists from CENTOGENE proved highly successful. These findings were published in Molecular Genetics & Genomic Medicine.

High scientific value of CentoMD®

Many of the as yet undescribed genetic disorders are ultra-rare. Identification of novel gene-disease associations thus relies on well-curated clinical-genetic data such as contained in CENTOGENE’s proprietary database CentoMD®. In a pertinent recent research project, CentoMD® was used to unravel a novel cause of neurodevelopmental delay. The findings were published in the prestigious American Journal of Human Genetics.

Many of the as yet undescribed genetic disorders are ultra-rare. Identification of novel gene-disease associations thus relies on well-curated clinical-genetic data such as contained in CENTOGENE’s proprietary database CentoMD®. In a pertinent recent research project, CentoMD® was used to unravel a novel cause of neurodevelopmental delay. The findings were published in the prestigious American Journal of Human Genetics.

Extension of rare disease therapeutic options

Treatment options for rare genetic diseases are often tested in cellular or animal models. CENTOGENE happily supports such projects in collaborative research settings. A recent example relates to a novel therapeutic cocktail for Niemann-Pick disease. Promising preliminary data were obtained in a mouse model, and published in Lipids in Health and Disease.

Treatment options for rare genetic diseases are often tested in cellular or animal models. CENTOGENE happily supports such projects in collaborative research settings. A recent example relates to a novel therapeutic cocktail for Niemann-Pick disease. Promising preliminary data were obtained in a mouse model, and published in Lipids in Health and Disease.

Novel disease gene discovered

The discovery of novel genetic disorders increasingly relies on large databases and on collaborative international efforts. CENTOGENE is proud to be part of numerous pertinent research endeavors. A recently accomplished corresponding project identified mutations in the PIGB gene as underlying a novel neuro-metabolic syndrome. The resulting study, which involved groups from ten countries, appeared in the highly prestigious American Journal of Human Genetics.

The discovery of novel genetic disorders increasingly relies on large databases and on collaborative international efforts. CENTOGENE is proud to be part of numerous pertinent research endeavors. A recently accomplished corresponding project identified mutations in the PIGB gene as underlying a novel neuro-metabolic syndrome. The resulting study, which involved groups from ten countries, appeared in the highly prestigious American Journal of Human Genetics.

Optimization of diagnostic yield

The genetic knowledge around rare hereditary diseases is rapidly increasing. Patients having received a negative diagnostic report may thus gain from a re-analysis of their exomes or genomes. A recent CENTOGENE-initiated study provided impressive evidence for this hypothesis. In a set of patients with neurodevelopmental disorders, for whom no diagnosis could be established prior to 2017, re-analysis revealed several potentially causative variants in disease genes described since. These findings were published in the June issue of Journal of Neurodevelopmental Disorders.

The genetic knowledge around rare hereditary diseases is rapidly increasing. Patients having received a negative diagnostic report may thus gain from a re-analysis of their exomes or genomes. A recent CENTOGENE-initiated study provided impressive evidence for this hypothesis. In a set of patients with neurodevelopmental disorders, for whom no diagnosis could be established prior to 2017, re-analysis revealed several potentially causative variants in disease genes described since. These findings were published in the June issue of Journal of Neurodevelopmental Disorders.

Utility of a CENTOGENE-developed biomarker

Metabolic biomarkers are well-accepted diagnostic tools, and may also qualify for monitoring purposes. The longitudinal dynamics of Lyso-Gb1, an established diagnostic biomarker for Gaucher disease (GD), was recently determined using CENTOGENE’s corresponding mass-spectrometry assay. Based on excellent prognostic performance of Lyso-Gb1, an inclusion in routine follow up of GD patients was recommended. The study was published in the June issue of International Journal of Molecular Sciences.

Metabolic biomarkers are well-accepted diagnostic tools, and may also qualify for monitoring purposes. The longitudinal dynamics of Lyso-Gb1, an established diagnostic biomarker for Gaucher disease (GD), was recently determined using CENTOGENE’s corresponding mass-spectrometry assay. Based on excellent prognostic performance of Lyso-Gb1, an inclusion in routine follow up of GD patients was recommended. The study was published in the June issue of International Journal of Molecular Sciences.

Biallelic variants in the transcription factor PAX7 are a new genetic cause of myopathy

The majority of novel disease genes is currently being identified in less well-investigated consanguineous populations. Based on its corresponding global positioning, CENTOGENE has been able to contribute significantly to such research projects. The most recent example is the discovery of recessive mutations in the transcription factor PAX7 to underlie a new form of muscle disease. The findings were published in Genetics in Medicine, one of the leading journals in the field.

Disease expressivity varies widely in many genetic disorders, and identifying the underlying modifiers holds great translational potential. Based on its resources as regards technologies and samples, CENTOGENE is uniquely positioned to significantly contribute to pertinent efforts. One recent example revealed a novel modifier of disease severity and cognitive dysfunction in X-linked dystonia-parkinsonism. The results were published in the highly prestigious journal Annals of Neurology.