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Use of WGS provides new diagnosis to determine genetic basis mitochondrial disease patients

TAIPEI, TAIWAN, Nov.30, 2021 - Mitochondria are the “energy plants” of our body. They process oxygen and convert substances from the foods we eat into energy needed to function. Mitochondrial diseases are chronic, genetic, often inherited disorders that occur when mitochondria can’t produce enough energy for the body to function properly.


Mitochondrial disease can affect the whole body and are difficult to diagnose Mitochondrial disease is one of the rare diseases. It can affect almost any part of the body, including the cells of the brain, nerves, muscles, kidneys, heart, liver, eyes, ears or pancreas. One in 5,000 people has mitochondrial disease. They are one of the most common inherited diseases but are difficult for clinicians to diagnose, not least because they can affect many different organs and resemble many other conditions. The diagnosis is so crucial for the patients and their families, unfortunately, recent genetic testing fails to diagnose around 40% of patients.



WGS can accelerate the diagnosis of Mitochondrial disease A new paper published in the BMJ, showed the silver lining to the patients' diagnoses that using Whole Genome Sequencing (WGS) can make more diagnoses faster. The paper was published by researchers from the MRC Mitochondrial Biology Unit and Departments of Clinical Neuroscience and Medical Genetics at the University of Cambridge. The purpose is to discover new disease genes and use WGS for genetic diagnosis for more patients.


WGS: an easier way to diagnosis Mitochondrial disease In total 345 participants with age 0 to 92, the WGS result showed that 62.5% of the diagnoses were non-mitochondrial disorders, with some having specific treatments. The reason is because the phenotype of mitochondrial diseases is similar to other diseases. In this project, the patients would only need to have a blood test for WGS analysis which would save the time and money to diagnose mitochondrial diseases.


The researchers made 37.5% of their diagnoses in genes known to cause mitochondrial disease. These diagnoses were nearly all unique to a particular participant family, reflecting the genetic diversity found in these disorders.

The 62.5% patients that were diagnosed as non-mitochondrial disorders had the similar features as mitochondrial diseases. The disorders would have been missed if the participants had only been investigated for mitochondrial disorders through muscle biopsy and/or a specific mitochondrial gene panel. It shows the possibility to have more precise diagnosis and treatment for the patients through WGS analysis.


Conclusion This study points out that the relatively high number of patients with probable or possible diagnoses reflects the need for greater investment into the analysis of functional effects of new genetic variants which could be the cause of disease, but it is not certain at present.It also argues that rapid trio whole genome sequencing should be offered to all acutely unwell individuals with suspected mitochondrial disorders, so that results can help guide clinical management.


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