A new study shows how errors in a specific gene can cause growth defects associated with a rare type of dwarfism.

During the study, an international team of scientists led by the University of Birmingham looked at genetic information from more than 250 people around the world with primordial dwarfism, a group of disorders characterised by short stature and an abnormally small head.

They found that 29 of the individuals had a defective version of a gene called DONSON.

Tests on cells growing in the laboratory revealed that this gene plays a crucial role in ensuring DNA is copied correctly when cells divide and grow.

Cells from patients with mutations in the DONSON gene had difficulty in efficiently replicating their DNA and protecting it from uncontrolled damage, ultimately leading to the growth defects typical of primordial dwarfism.

Most children with primordial dwarfism are not diagnosed until they are around three years old, and doctors are often unable to pinpoint the causes. This research raises the potential of more accurate diagnoses for patients with genetic microcephaly, in addition to providing an insight into how similar rare hereditary diseases are caused.

Professor Grant Stewart, from the Institute of Cancer and Genomic Sciences at the University of Birmingham, says: ‘Despite DNA replication being a process that is fundamental to life, there is still a lot we don’t know. This research sheds new light on the mechanisms underlying DNA replication, and the effect on human health when this process goes wrong.’

Professor Andrew Jackson, of the University of Edinburgh’s Institute for Genetics and Molecular Medicine, says:  ‘Identification of DONSON as a new microcephaly gene has given us new insights into how the genome is protected during DNA replication, and has only been possible through the close collaboration and contributions of clinicians and scientists from many countries around the world.’

Professor Christopher Mathew, from the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas’ and King’s College London, adds: ‘This is a good example of how unravelling the genetics of rare human disorders can provide profound insight into basic biological processes.’

This study was the result of collaboration by researchers from institutions including the University of Birmingham (Professor Grant S Stewart), the University of Edinburgh (Professor Andrew P Jackson), Kings College London (Professor Christopher G Mathew) and the King Faisal Specialist Hospital and Research Center in Saudi Arabia (Professor Fowzan S Alkuraya).

The research was jointly funded by the Birmingham Children’s Hospital Research Foundation, Cancer Research UK, the European Research Council, the Lister Institute for Preventative Medicine, the NIHR Biomedical Research Centre at Guy’s and St Thomas’ and King’s College London, the King Abdulaziz City for Science and Technology, and the Medical Research Council.