Health

Genetic disease is more likely in the children of older fathers – but why? Part of the answer may be that benign testicular tumours, more common in older men, give rise to sperm containing disease-causing mutations.

Anne Goriely of the University of Oxford and her colleagues took tumour cells from men with benign testicular tumours and looked for specific mutations in the FGFR3 and HRAS genes. These mutations have been linked to rare developmental diseases such as achondroplasia, or "dwarfism", and Costello syndrome, a condition that involves skin deformities and mental retardation. They have also been linked to some stillbirths.

The researchers found the same mutations in the tumour cells, but not in normal sperm-producing cells located nearby. They concluded that the sperm made by these cells contained the disease-containing mutations and that the mutations may be driving the growth of the tumours.

Older men are more likely to have testicular tumour cells, so more of their sperm-producing cells will contain these mutations.

A lot of men have these cells without knowing it because they often fail to develop into discernible tumours. "In most cases we think the body's growth control mechanisms eventually stop the cells from proliferating further, but in occasional cases where additional mutations occur in the clump of cells, a tumour will eventually develop," says Andrew Wilkie also of the University of Oxford, who supervised the work.

He likens them to moles in the skin, which are also benign tumours that stop growing. "But being located in the testicle, these cells also make sperm – causing children to be born with a variety of serious conditions," Wilkie says.

Because all ageing men may be subject to this process, screening is unlikely to be much help.

Journal Reference: Nature Genetics, DOI: 10.1038/ng.470

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