MRC Human Genetics Unit
Medical Research Council Human Genetics Unit


Mutations in TOP3A Cause a Bloom Syndrome-like Disorder

Findings may help guide clinical care: July 2018

sister chromatid segregation defects



Microcephalic primordial dwarfism (MPD) is a group of conditions in  which growth is markedly restricted from early development, alongside smaller head circumference (microcephaly). Bloom syndrome is also  associated with prenatal growth restriction, short stature, and  microcephaly and results in higher cancer risk. Andrew Jackson,  Carol-Anne Martin and colleagues have identified mutations in the TOP3A gene in people with a Bloom-like syndrome. These mutations affect the ability of the cells to untangle DNA during cell divison, affecting cell growth as in Bloom syndrome. However, unlike those with Bloom syndrome, several children with the TOP3A mutations also developed a mitochondrial cardiomyopathy (mitochondria are the powerhouses of the cell. This work provides additional genetic tests for those with Bloom or Bloom-like syndromes and will help clinical management, for example leading to careful monitoring of the heart in children who have TOP3A mutations.


Original research paper:

Andrew Jackson Research Group