Sequencing can boost genetic diagnosis for learning disability

30 April 2012

Efforts to identify genetic causes of learning disability suggest much higher rates of diagnosis may be feasible.
Learning disability and developmental delay are relatively common, affecting 1-3% of the general population, and genetic causes can underlie up to around half of all cases, depending on the severity of the condition. Diagnosis can improve care by avoiding unnecessary medical investigations, predicting the risk to future children and improving access to social care.
Advances in genomics such as microarrays have made it increasingly feasible to identify genetic features linked to learning disability (see previous news). Now, large-scale clinical genome sequencing projects are seeking to identify many more such variants, to improve diagnosis and in the longer-term, hopefully inform the development of treatments.
The UK Deciphering Developmental Disorders (DDD) project (see previous news) is using DNA from 12,000 affected children and their parents for array analysis and exome sequencing, with similar projects underway in many other countries. A Netherlands initiative has reported the identification of genetic causes in about 40% of children with learning disability, based on exome sequencing of the children and parents, a substantial increase over typical diagnosis rates of well below 20%.
Comment: Such research raises concerns; it is not always easy to determine which mutations are causal, and which are not. Sequencing unaffected parents allows the elimination of shared, familial genetic changes; changes in genes known to be involved in brain development and function, or which have previously been associated with forms of learning disability are likely candidates. However, until the same mutation is recognised in different patients with similar disabilities (but not in unaffected individuals), designation as a cause is not certain.

Nevertheless, it seems likely that the next few years will yield valuable information that will offer improved diagnosis for affected families as genomic medicine moves into the clinic.