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Developmental disorders linked to 28 newly associated genes

19 October 2020
Appeared in BioNews 1068

285 genes have been identified as being causally implicated in developmental disorders, 28 of which have never previously been linked with such conditions.

The large collaborative study recently published in Nature describes how the authors created a genetic database to analyse developmental disorders by integrating anonymised healthcare records with ongoing genetic research. Genetic information from children with developmental disorders was grouped with that of the child's parents and evaluated in 'trios'. Over 31,058 exome sequence trios were interrogated to identify de novo mutations – genetic mutations present in the affected child, but not in either parent.  

'From previous studies we know that certain genes and types of mutation are more strongly linked to developmental disorders, which has allowed us to narrow our search. Combined with a much larger dataset, this has enabled us to identify 28 novel genes associated with developmental disorders' said Dr Kaitlin Samocha, co-lead author of the study.

De novo mutations are common. In fact, each one of us carries approximately 60 spontaneously altered genes. While most de novo mutations are harmless, they are a recognised cause of developmental disorders. However, many developmental disorders are rare, which often makes it difficult for researchers to statistically prove that an identified mutation is significantly associated with a certain condition. By gaining access to health records, coupled with the genetic data, the team was able to improve the statistical power of their research.

These findings will benefit hundreds of families caring for children with rare developmental disorders, by finally providing them with an affirmative diagnosis. Dr Helen Firth, consultant clinical geneticist at Addenbrooke's Hospital in Cambridge explains why this is so important:

'Caring for a child with a developmental disorder can be extremely challenging for a family, particularly when their child's doctors don't know what is causing their condition and are unable to make a diagnosis. A diagnosis can help families to access support networks, inform treatment for their child and help them to understand the risk for any further children they might have.'

Statistical modelling of their combined database revealed that there are potentially a further 1000 undiscovered genes related to development disorders. The authors have highlighted that in order to identify such genes, they require a volume of data which is much greater than that which is currently available. This, they argue, is only achievable by improving access to further healthcare information.

'This study has really shown the benefits of access to healthcare data, not least to the approximately 500 families living with a developmental disorder who had not been able to get a diagnosis until now. But our findings also estimate that we require ten times as much data to be able to identify all the genes linked to developmental disorders. As such, greater access to anonymised patient data is crucial to our understanding of these conditions and our ability to help the families living with them,' said Professor Matthew Hurles, corresponding author of the study from the Wellcome Sanger Institute.

Developmental disorder study identifies 28 novel disease genes
Genome Web |  14 October 2020
Evidence for 28 genetic disorders discovered by combining healthcare and research data
Nature |  14 October 2020
Study linking 28 genes to developmental disorders will mean diagnoses for around 500 families
Wellcome Sanger Institute |  14 October 2020
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