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Genetic metabolic disorder linked with DNA mutation, claims study


Researchers have identified that genetic is linked with

According to the research published in of Medicine, inherited metabolic disorders- in which the body can't break down specific nutrients from leading to a range of serious problems- are often caused by a defective

In the study by BC Children's Hospital, the (UBC) and an international team of researchers, researchers found an unusual genetic behind three children's undiagnosed, degenerative conditions: a repeat expansion of

In this specific mutation, the appears undamaged but does not function because the adjacent to it has extended several hundred times its normal length.

"To detect this kind of DNA multiplication, you can only use whole-genome sequencing and have to search through billions of pieces of DNA; it's truly a search for the needle in the haystack," said the lead author, Dr

"With our new approach we have finally solved our mystery cases, and we now expect to find the genetic cause of other, as of now unexplained, genetic metabolic diseases," Karnebeek added.

To date, DNA repeat expansions have been linked to approximately 30

"For kids with and their families, finding the root causes of their is tremendously important," said Dr Wyeth Wasserman, a of the study.

"A diagnosis gives us the potential to intervene, relieves undeserved parental guilt, and provides insights into more common diseases," Wasserman added.

For a child with an medical condition, a diagnosis lays the groundwork for further research that could lead to new interventions such as therapy aimed at 'turning on' the impaired gene, dietary modification or supplements that provide the nutrients the body is missing.

Effective treatment can slow or stop damaging symptoms, improving the quality of life of children with and their families.

In this study, initial work by Karnebeek and her research team narrowed the search for the genetic causes of this to key areas of the genome.

However, after further investigations using exome sequencing and whole genome sequencing, the international research team couldn't pinpoint the error in the DNA.

It's here that researchers at BC Children's took a novel approach. Through in-depth, manual analysis and the use of emerging tools and techniques study co-authors, Dr and discovered and confirmed that the gene responsible for the was intact but a repeat expansion error prevented it from functioning.

"In our search, we focused on variations that would have been hard to discover through exome sequencing," said Drogemoller.

"After months of experimenting with various different analyses, we finally uncovered this novel genetic variant by using new targeted approaches aimed at identifying DNA repeat expansions," added Drogemoller.

"These findings were made possible by a multidisciplinary approach and advances in technology, techniques and software. It wouldn't have been possible as recently as two years ago and, most importantly, it shows us what to look for in other undiagnosed cases," said Richmond.

The gene identified as the cause of this is an enzyme that enables the body to turn an amino acid called glutamine into glutamate. More work is needed to determine how exactly this genetic error leads to disease, but it's likely that either a build-up of glutamine or the lack of glutamate caused the children's serious developmental delays and disabilities including difficulty with language, speech, balance and coordination.

Through collaborations with sequencing consortiums around the world, researchers were able to confirm that this particular repeat expansion was found in only 1 in 8,000 people, establishing the as very rare.

(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)

First Published: Tue, April 16 2019. 12:59 IST