A new study has identified rare changes in a particular gene, CDK4, which lead to reduced growth in individuals, including smaller brain size and shorter height. MRI scan of age-matched control (4 years 8 months) and affected individuals with a CDK4 variant The CDK4 gene encodes a key protein which is important in controlling how our cells grow and replicate. The study, co-led by researchers from the Institute of Genetics and Cancer (IGC) and the University of São Paulo in Brazil, looked at skin cells from people with these changes and used molecular and cell biology approaches to show how the genetic mutations lead to a large reduction in the amount of CDK4 protein able to function. Loss of this key protein results in defects in the cell’s ability to grow and replicate. The collaboration between researchers in Edinburgh and Brazil came about after both labs found the CDK4 mutations independently and were then matched using GeneMatcher – a website which enables connections between patients, their families, clinicians and researchers worldwide with an interest in the same gene or genes. These findings show that CDK4 is important for cell growth and therefore for brain and body size during development. This is the first time that mutations in the CDK4 gene have been found to cause microcephaly and short stature. We have so far only identified two families worldwide that are affected by these mutations. Publishing these findings could enable other doctors and researchers to identify similar mutations in individuals with microcephaly. For individuals and their families affected by these genetic changes, gene testing is now possible, enabling them to know for definite how the condition is inherited and will also assist their clinicians in ongoing management. Professor Andrew Jackson MRC Human Genetics Unit The paper is published in Genes & Development. Read the study (external link) Andrew Jackson Research Group Tags 2025 Publication date 17 Apr, 2025
