Sam was a 2-year-old boy (not participant’s real name or photo) that had to deal with more in his short life than most adults deal with in a lifetime. When he was born, it was quickly realised he had a defect in his heart and a smaller than normal head. When doctors looked more closely at his brain, they discovered that the structure of his brain was different. Over time Sam developed epilepsy and it became clear he would have severe challenges ahead. Numerous doctors attempted to identify what was wrong with Sam and lots of genetic tests were ordered. All came back negative.

In 2018, doctors at CHI at Temple Street approached the research team at Genomics Medicine Ireland (now Genuity Science) to review Sam’s case. Since 2017, a team of dedicated research scientists and bioinformaticians at Genuity Science have been using an advanced genetic technology called whole genome sequencing to help doctors diagnose children with rare disorders.

Sam and his parents’ entire genetic code was sequenced at Genuity Science’s state-of-the-art genomics centre located at their Cherrywood site in Dublin, Ireland. Research scientists at Genuity Science used clinical data provided by Sam’s doctor to direct their analysis of his genome. The first stage of analysis identified 86 variants in a very specific subset of Sam’s genes related to his signs and symptoms. The team then reviewed each variant individually to see if any of them could explain Sam’s disorder.

Eventually, the Genuity Science research team identified a genetic explanation for Sam’s condition. They found two variants in a gene called TRIT1. TRIT1 plays an important role in making sure that the mitochondria in all the cells of our bodies are made and perform correctly. All of us have two copies of the TRIT1 gene, but Sam’s variants mean that he has no functioning copy of this gene. He inherited one variant copy from his mother, and a second variant copy from his father. Genuity Science discussed this result with Sam’s doctor to make sure that Sam’s clinical signs and symptoms were consistent with those of other children who have similar variants in the TRIT1 gene. Sam’s doctor agreed and after confirming the variants in a diagnostic lab, communicated the findings to Sam’s parents. Sam had a 25% chance of acquiring these variants from his parents, and they now know that they have a similar risk for any future pregnancies. Sam is only the eighth child in the world to be clinically diagnosed with this disorder. Sam’s clinical signs and symptoms were more severe than the other children described in the literature. Genuity Science and CHI at Temple Street shared Sam’s genetic variants and clinical features with the wider research community so that we all can learn more about this devastating condition.

Sadly, Sam passed away at the age of 2. For many of the ultra-rare disorders that we identify, there is no treatment currently available. However, for children with undiagnosed disorders and their families it is important that they have a diagnosis and an understanding of the cause of their condition. Having this knowledge can help them make decisions about the future for their families and allows them the opportunity to reach out to families in the same situation for support and advice.