FGF14

FRAMINGHAM, Mass.--(BUSINESS WIRE)-- Variantyx, a leader in genomic precision medicine, today announced that the set of short tandem repeat (STR) expansions detected by its Genomic Unity® line of whole genome-based tests has been expanded. With these additions, Variantyx becomes one of the first laboratories to offer testing for two recently characterized ataxia variants: the biallelic AAGGG expansion in RFC1 that causes cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and the monoallelic, deep intronic GAA expansion in FGF14 that causes spinocerebellar ataxia 27B (SCA27B). “Short tandem repeat gene analysis and interpretation has always been challenging in clinical diagnostics,” said Christine Stanley, PhD, FACMG, Chief Director of Clinical Genomics at Variantyx. “Because the entire genome is sequenced, Genomic Unity® testing has the ability to detect a broader range of STRs from a single sample compared to targeted technologies utilized by other laboratories. At Variantyx we’re committed to continually extending the detection capabilities of our whole genome-based platform and are pleased to now be able to provide extended analysis and interpretation of STRs which is expected to result in additional diagnostic answers for patients.” The product line now analyzes an industry-leading 37 repeat expansions, collectively enabling the genetic diagnosis of late-onset neuropathies, neuromuscular disorders and movement disorders - particularly ataxias - as well as early-onset disorders, including those with symptoms of epilepsy and intellectual disability. The additional detection capabilities are automatically included in all Genomic Unity® comprehensive analyses and relevant targeted analyses. About Variantyx Variantyx is an award-winning, technology-driven precision medicine company providing disruptive solutions for the genetic disorders, reproductive health, and precision oncology markets. The proprietary whole genome analysis platforms developed by Variantyx allow clinicians and patients to better understand a person’s genetic makeup, leading to unmatched diagnostic capabilities and improved personalized treatment recommendations. For more information, please visit . View source version on businesswire.com: Contacts Haim Neerman Haim.neerman@variantyx.com (617) 209-2090 Source: Variantyx View this news release online at:

A new study reports the identification of a previously unknown genetic cause of a late-onset cerebellar ataxia, a discovery that will improve diagnosis and open new treatment avenues for this progressive condition. A new study published on Dec. 14, 2022 in the New England Journal of Medicine reports the identification of a previously unknown genetic cause of a late-onset cerebellar ataxia, a discovery that will improve diagnosis and open new treatment avenues for this progressive condition. Late-onset cerebellar ataxias (LOCA) are a heterogenous group of neurodegenerative diseases that manifest in adulthood with unsteadiness. One to three in 100,000 people worldwide will develop a late-onset ataxia. Until recently, most patients with late-onset ataxia had remained without a genetic diagnosis. An international team led by Dr. Bernard Brais, a neurologist and researcher at The Neuro (Montreal Neurological Institute-Hospital) of McGill University and Dr. Stephan Züchner of the University of Miami's Miller School of Medicine, in collaboration with neurologists from the Universities of Montreal and Sherbrooke, studied a group of 66 Quebec patients from different families who had late-onset ataxia for which an underlying genetic cause had not yet been found. Using the most advanced genetic technologies, the team found that 40 (61 per cent) of the patients carried the same novel disease-causing variant in the gene FGF14, making it the most common genetic cause of late-onset ataxia in Quebec. They found that a small stretch of repetitive DNA underwent a large size increase in patients, a phenomenon known as repeat expansion. To confirm their initial findings, the team reached out to international collaborators in Tübingen in Germany, Perth in Australia, London in the United Kingdom, and Bengaluru in India. They found that 10-18 per cent of LOCA patients in these independent cohorts also carried the same FGF14 error. These results confirmed that a repeat expansion in FGF14 is one of the most common genetic cause of late-onset ataxia described to date. Going beyond gene discovery, the team also studied brains from deceased patients and neurons derived from patients and found that the error causes decreased expression of the gene and its protein. Patients with a FGF14-related late-onset ataxia experience unsteadiness (ataxia) usually beginning in their fifties. The disease may start with short episodes of ataxia that can be precipitated by exercise and alcohol intake. The coordination problems become permanent on average around 59 years old. The disease usually progresses slowly and affects walking, speech and hand coordination. Often with time it requires walking aids. The condition is most often transmitted from an affected parent although it can appear in families with no previous history of ataxia. The FGF14 GAA repeated sequence of the mutation raises much interest, since it is identical to the one causing Friedreich ataxia in the FXN gene, the most common cause of autosomal recessive ataxia worldwide. Because of this similarity, it is possible that some of the new treatments under development for Friedreich ataxia may be used to treat patients with an expansion in FGF14. This study also suggests that patients may benefit from a drug called aminopyridine that is already marketed for other neurological conditions. This is especially promising since some patients with an expansion in FGF14 have responded well to this treatment. "This opens the door to a clinical trial of this drug in these patients," says Dr. Brais. "It's great news for patients in Canada and worldwide. It also makes genetic testing possible so people and families can arrive at the end of their long diagnostic journey." Published in the New England Journal of Medicine on Dec. 14, 2022, this study was funded with support from many national agencies, including the NIH, the Fondation Groupe Monaco and the Montreal General Hospital Foundation.

Findings highlight early detection potential of methylation markers, demonstrating opportunity for improved survival rates of CRC patients CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Universal Diagnostics (Universal DX), a bioinformatics and multi-omics company on a mission to transform cancer into a curable disease, today announced the results of a study evaluating putative methylation markers in biological context of early colorectal cancer (CRC) development. Universal DX has previously shown that non-invasive blood testing can be used to detect CRC and pre-cancerous advanced adenomas (AA) through both analysis of cell-free circulating tumor DNA (ctDNA) methylation, fragmentation and microbiome patterns with single targeted sequencing analysis and combining it with advanced computational biology and machine learning algorithms. Today’s news is the latest in a series of findings from Universal DX, extending early-stage colorectal cancer detection to prognostics and stratification, which could lead to better outcomes and improved survival rates. “This newest study underscores the robustness and validity of our previous results, by adding more biological value to the individual methylation marker regions,” said Christian Hense, COO at Universal DX. “Investigating their impact on gene expression and putting these biomarkers in the context of biological pathways allows for better understanding of the behavior of early cancer. Extending early detection potential of the markers to further prognostics and stratification could lead to improved survival outcomes of the patients as well as potentially serve as interesting new treatment targets in the future. Every step in our research gets us closer to a day where cancer is a curable disease and we can save more lives.” Study results: Differential signal was observed between AA and NAT and CRC and adjacent normal tissue, indicating biological signal change with adenoma progression to cancer. Hierarchical clustering identified 3 distinct classes of patients based on methylation levels. KEGG pathway analysis revealed that the top pathways involved were axonal guidance, ephrin receptor signaling, epithelial-mesenchymal transition and FGF signaling, all which play a significant role in the context of cancer development and progression. Correlation of methylation signal to transcriptomics data from The Cancer Genome Atlas (TCGA) COAD and READ cohorts showed significant correlation to dysregulation of the gene expression, indicating the functional relevance of the gene methylation. Targeted methylation sequencing on plasma samples of patients with early stage (I-IIA) colorectal cancer (26 patients from Ukraine and Germany) and age and gender matching colonoscopy-verified controls (from same cohort), showed high individual marker accuracy with AUC > 0.73. Kaplan-Meier analysis showed significant correlation to patients’ 5- year survival prediction linked to 3 genes: FGF14 (p=0.025, HR = 1.75), DPY19L2P1 (p=0.012, HR = 1.86), PTPRO (p=0.046, HR = 1.63). Universal DX leverages proprietary, state-of-the-art computational biology tools combined with a targeted next generation sequencing assay platform that allows for simultaneous detection of methylation, fragmentation and microbiome signals for highly-sensitive cancer signal scoring of cell-free DNA regions linked to cancer of interest. Hense continued: “CRC is one of the deadliest cancers in the United States. The current methods of biomarker-based tests to screen for CRC are still extremely limited. At Universal DX, we are on a mission to find new and better methods. We know early detection is one of the most powerful tools for improving survival rates, so identifying these markers could be the next step towards earlier – and easier – detection.” Universal DX will present its findings live at the AACR special conference on Precisions, Prevention, Early Detection, and Interception of Cancer in Austin, TX November 17-19. About Universal Diagnostics Universal DX is on a mission to transform cancer into a curable disease. With its multi-omics + computational biology + machine learning approach, it is cracking the code to “true” early cancer detection, having identified the specific cfDNA sequence regions that capture cancer’s earliest signal with +90% accuracy. Its first single-draw blood test, Signal-C, accurately detects colorectal cancer with a sensitivity rate of 92% and specificity rate of 97%, with extraordinary accuracy for earlier stages (89%/97%). The company’s multi-cancer platform seeks to identify the unique DNA sequence regions associated with high-burden cancers, such as pancreatic, liver and stomach, with high sensitivity and tissue-of-origin specificity. For more information about the company, visit .