Calgary Next Generation DNA Sequencing Method for Mitochondrial Disease Diagnosis

Research Update – May 2014


Grant and Project Information

Date:  March 2012

Award:  CIBC provided a $20,000 grant to MitoCanada in March 2012, which was subsequently granted (along with an additional $5,000 from MitoCanada) to The Alberta Children’s Hospital Research Institute (ACHRI) which provided matching funds.  For 2012, the total award was $50,000.  For 2013, CIBC is donating $25,000 directly to ACHRI.

Calgary Next Generation DNA Sequencing Method for Mitochondrial Disease Diagnosis

Aneal Khan, M.D.
Department of Medical Genetics and Pediatrics at the University of Calgary, Alberta Children’s Hospital 

The CIBC grant to MitoCanada will be granted to Dr. Aneal Khan, Department of Medical Genetics and Pediatrics at the University of Calgary, Alberta Children’s Hospital, to expand the platform to diagnose Mitochondrial Disease in children using the Next Generation sequencing method (NGS). Mitochondrial disease causes abnormal function of the heart, brain, liver and muscles leading to poor development, strokes, multiple body dysfunctions and a shortened lifespan.  Mitochondrial disease affects 1 in 5000 people.  More than 1,000 genes are involved in mitochondrial function and previous methods of diagnosis involved invasive tissue biopsy, could only test a handful of genes, put patients at risk for procedural complications and could only make a diagnosis in a small number of cases.  The NGS Project is a clinical platform using state-of-the-art technology for diagnosing Mitochondrial Disease and is the first of its kind in Alberta and Canada. NGS does not require painful and risky tissue biopsies and can be performed on DNA obtained from either a blood test or a cheek swab. The uniqueness of the project at Alberta Children’s Hospital aims to bring this technology to the bedside and make it easy to use by doctors who have patients with diseases for which a diagnosis has been elusive. By making a diagnosis of Mitochondrial Disease, doctors can make more precise decisions about treatment rather than wait the months or years to obtain an answer using traditional methods. As part of the initiative, a total of 8 patients were tested using NGS in Calgary.  In addition, 4 patients were previously sequenced through an initial pilot project bring the total number of patients who have had NGS to 12.

The impact of NGS in the lives of patients with Mitochondrial Disease cannot be overstated. As an example, from the 2012 grant from the CIBC, Dr. Khan recently identified a gene causing Mitochondrial Disease in an 8 year-old girl who has waited her entire life to find a diagnosis for a liver condition from which she nearly died at 4 months of age. It was not known whether the complications would lead to more medical problems in the future or what the future held for her. The NGS data identified a gene which has been shown to cause the same liver problems in infancy but most children gradually improved over time which means the prospects for this child to have a long term recovery are very good and she does not need to have another liver biopsy. In other patients, some of them were thought to have multiple sclerosis has been found to have a gene mutation causing Mitochondrial Disease. In another family, who had one child die of a severe undiagnosed disease and a second child also showing the same deterioration, a gene appears to have been identified that might provide a diagnosis and an easier method to diagnose the disease in other children or in future pregnancies.

In the future, development of NGS in hospital clinics, such as at Alberta Children’s Hospital, will allow doctors to shorten the diagnostic time from months and years to weeks, avoid costly, painful and risky procedures to get tissues for diagnosis and overall be able to start treatment in patients earlier. The CIBC grant has already produced outcomes in a short period of time that have allowed Calgary doctors to advance the application of NGS thus benefitting families looking for an answer as to why their children are sick. The 2013 funds will expand this great work and make a significant impact to children suffering from complex metabolic issues and Mitochondrial Disease in Calgary.

See Also:  Letter from Alberta Children’s Hospital to MitoCanada