Centogene Biodatabank Reveals Unique Genetic Variants in World's Largest Niemann-Pick Type C1 Disease Cohort

CENTOGENE N.V. recently announced the publication of a landmark study titled At a glance: the largest Niemann-Pick type C1 cohort with 602 patients diagnosed over 15 years. Recently published in the European Journal of Human Genetics, one of the world’s leading medical genetic journals, the study represents the largest and most heterogeneous Niemann-Pick type C1 disease (NPC1) cohort, with 602 patients referred from 47 countries.

NPC1 is a rare and severe autosomal recessive disorder, characterized by a range of neurovisceral clinical manifestations and a fatal outcome with no effective treatment to date. To gain a deeper understanding of the disease, researchers carried out an analysis using the CENTOGENE Biodatabank, which included clinical, genetic, and biomarker data from NPC1 patients from the past 15 years. The study’s findings reveal groundbreaking insights into the clinical and metabolic patterns of NPC1.

“The publication of this landmark study marks a pivotal moment in our understanding of Niemann-Pick type C1 disease patients,” said Professor Peter Bauer, CENTOGENE’s Chief Medical and Genomic Officer. “We believe that data enables us to better understand a disease with very diverse symptoms and clinical courses, and this study puts us on the right path to identifying potential therapeutic strategies with pharma partners.”

The analysis of the data captured in the CENTOGENE Biodatabank revealed 287 unique Pathogenic/Likely Pathogenic (P/LP) variants, with 73 having not been described previously. Additionally, researchers identified variant-linked patterns of symptoms and manifestations by leveraging Human Phenotype Ontology (HPO) terms. Furthermore, these results suggest that in addition to its utility to classify and report variants, the biomarker N-palmitoyl-O-phosphocholineserine ((PPCS), formerly known as lyso-SM-509), might serve to indicate disease severity/progression. In analyzing the data, CENTOGENE was able to establish novel genotype-phenotype relationships and illustrate the value of combined genetic and biomarker testing to diagnose and increase the understanding of NPC1.

“The study results are a perfect reflection of the significance of data and establishing a holistic diagnosis,” added Dr. Aida Bertoli-Avella, Head of Research Data Analysis at CENTOGENE. “By assembling the world’s largest NPC1 cohort, we have gained unprecedented insights that will fuel further research, clinical development, and ultimately, improved patient outcomes.”

To read the full study, visit: https://link.centogene.com/npc1-publication

The genetic diagnosis of the 602 patients from 47 countries was established using a combination of genetic and biomarker testing, alongside Human Phenotype Ontology (HPO) terms. In doing so, CENTOGENE confirmed the high allelic heterogeneity of NPC1 with 287 unique Pathogenic/Likely Pathogenic (P/LP) variants being identified. Seventy-three of these were novel, unpublished causative variants. This high number of novel variants is likely due to the inclusion of patients from populations that are usually underrepresented in scientific literature and public genetic databases, such as Africa, the Middle East, and Latin America.

To date, this is the largest dataset described for NPC1, with other large cohorts including a study from the United Kingdom that describes 114 patients, a study from the International Niemann-Pick Disease Registry (INPDR) describing 97 patients having NPC1 variants, and a study describing 105 NPC1 patients from Italy.

To read more about the study published in the European Journal of Human Genetics, visit: https://link.centogene.com/npc1-publication

CENTOGENE’s mission is to provide data-driven, life-changing answers to patients, physicians, and pharma companies for rare and neurodegenerative diseases. We integrate multiomic technologies with the CENTOGENE Biodatabank – providing dimensional analysis to guide the next generation of precision medicine. Our unique approach enables rapid and reliable diagnosis for patients, supports a more precise physician understanding of disease states, and accelerates and de-risks targeted pharma drug discovery, development, and commercialization.

Since our founding in 2006, CENTOGENE has been offering rapid and reliable diagnosis – building a network of approximately 30,000 active physicians. Our ISO, CAP, and CLIA certified multiomic reference laboratories in Germany utilize Phenomic, Genomic, Transcriptomic, Epigenomic, Proteomic, and Metabolomic datasets. This data is captured in our CENTOGENE Biodatabank, with over 750,000 patients represented from over 120 highly diverse countries, over 70% of whom are of non-European descent. To date, the CENTOGENE Biodatabank has contributed to generating novel insights for more than 275 peer- reviewed publications.

By translating our data and expertise into tangible insights, we have supported over 50 collaborations with pharma partners. Together, we accelerate and de-risk drug discovery, development, and commercialization in target and drug screening, clinical development, market access and expansion, as well as offering CENTOGENE Biodata Licenses and Insight Reports to enable a world healed of all rare and neurodegenerative diseases. For more information, visit www.centogene.com.