Whole genome sequencing for copy number variant detection to improve diagnosis and management of rare diseases
Genes are instructions which control development and normal cell function. We usually have two copies of every gene; one copy from each parent. Copy number variants (CNVs) are extra or missing copies of genes. These can be part of normal human genetic variation but can also cause genetic disorders. Identifying a CNV can help with diagnosis and treatment of associated medical problems.
There are different ways of looking for CNVs in the laboratory. Traditional methods of doing this can sometimes miss CNVs, or if found, they can be difficult to interpret. One new way of doing testing is called whole genome sequencing (WGS).
- In the first case, WGS identified an extra copy of a gene called PRKN. This helped explain the cause of young onset Parkinson disease in the affected individual.
- In the second case, WGS showed there was a missing copy of the TAOK1 gene, which was the cause of developmental problems in the child concerned.
- In the third case, WGS allowed a diagnosis of a rare condition called Usmani-Riazuddin syndrome to be made. This is due to a missing copy of the AP1G1 gene.
We therefore show that in some cases, WGS can be better at finding CNVs than other methods of laboratory testing. This can help make a genetic diagnosis. Knowing the genetic diagnosis can improve medical treatment for the affected person, and can also help with counselling about the risks to other family members.
