The molecular basis for another rare disease has been identified by our exome sequencing programme.
BRC researchers have discovered that Wiedemann-Steiner Syndrome (WSS) is the result of newly arising mutations in the gene MLL.
The team sequenced the exomes of 6 affected individuals and found that 5 had a mutation in the MLL gene. The gene codes for a histone methyltransferase enzyme, a protein that modifies the packaging of DNA.
“Histone modification enzymes are an interesting family of proteins. Mutations in these genes have recently been shown to be the cause of several developmental disorders, including our recent discovery in Genitopatellar Syndrome” says Dr Michael Simpson who leads the BRC's exome sequencing programme. “The severe symptoms associated with these disorders demonstrate how the correct packaging of DNA by this family of proteins is critical during development."
WSS is a rare condition, with less than one affected individual per 100,000. It is associated with mental retardation, short stature, characteristic facial features, and excessive hair on the elbows and back.
WSS has been known about for over a decade, but it was impossible to determine the molecular basis using the traditional family pedigree approach. This is because the mutation spontaneously occurs in the affected individuals, it is not inherited from the parents.
The new DNA sequencing technology used by the BRC’s exome sequencing programme is the only way the genetic basis of WSS could have been identified.
Reference: WD Jones et al, De Novo Mutations in MLL Cause Wiedemann-Steiner Syndrome, Am J Human Genetics (July 2012)
Exome sequencing (also known as targeted exome capture) is the selective sequencing of only the portions of a gene that code for a protein. It is a cost-effective alternative to sequencing the whole genome. The coding portions of genes only account for about 1% of the human genome, but is where about 85% of disease-causing mutations occur.
Posted on Friday 20th July 2012