For most people with intellectual disabilities (ID), and their families, knowing the genetic cause of a disability would be of great value, offering new understanding and possibilities for improved care.
Standard chromosome analysis methods help diagnose some disabilities, such as Down syndrome. But causes of many other forms of intellectual disability that affect millions of children can’t be found this way. Not knowing what caused an ID and what health issues lie ahead is a hardship for many parents.
University of British Columbia researcher Evica Rajcan-Separovic has taken on the challenge of finding genetic causes for IDs that currently defy detection, leading eventually to improved care.
With co-investigator Dr. Suzanne Lewis, a UBC clinical professor in Medical Genetics, support from BC’s Children’s Hospital, Child and Family Research Institute and many genetic centers countrywide, Rajcan-Separovic assembled a research group of 1,000 children. Most of the children were from B.C. and were identified as having an ID with no known cause.
“Previously, children with developmental delay would only have chromosome testing,” said Rajcan-Separovic. “But microscope analysis is low resolution and an abnormality of a small segment of DNA can easily be missed.”
To get a better look at chromosomes the team initially went beyond microscope analysis to the intricate process of chromosome microarray analysis.
A patient’s DNA is compared segment by segment to normal DNA. Mutations such as deleted or duplicate genes are highlighted by a computer analysis.
Using microarray analysis, the team found that 150 of the 1,000 ID’s tested did indeed have genetic defects, which could be the cause of childrens’ developmental delay.
Strikingly, two of the children had hidden genetic abnormalities that became key element to Rajcan-Separovic’s breakthrough research.
The pair, an unrelated girl and boy from B.C., had the same genetic defect. In the long thread-like structure of a single chromosome, the microarray revealed that a single, almost identical, segment of genetic material was missing in both children. The pair shared abnormalities in facial features, had visual impairment, behavioural issues and range of other common physical abnormalities and health issues.
“The geneticists who saw the two children commented that they resembled each other as if they were siblings,” said Rajcan-Separovic.
The childrens’ matching genomic and clinical data, led to establishment of a new microdeletion syndrome of ID. After the research was published, geneticists around the world identified 20 new identical cases, creating a new source of shared information for the families. “If you know there is a possibility of early onset of health issues, for example impaired vision or kidney problems, in a child with a syndromic ID, measures can be taken to possibly avert or minimize those adverse outcomes,” says Rajcan-Separovic.
The next step for the UBC team is unravelling the ID mystery for the remaining 850 children in their group. No cause, genetic or otherwise has been found for their disabilities. The researchers are stepping up their investigative technology to use next generation genetic sequencing. This approach will detect abnormalities at a nucleotide level, the smallest component of a single DNA molecule
Dr Rajcan-Separovic is an Associate Professor in the Department of Pathology, UBC, Clinical Cytogeneticist in the Department of Pathology in Children’s and Women’s Hospital and Scientist at Child and Family Research Institute.