A new approach in the genetic diagnosis of rare diseases
Karol looks at her son Mark and only sees his happy face. However, to anyone else, it is evident that Mark has a slightly smaller head than usual, his muscles are hypotonic, his lips and tongue are more prominent, and he sometimes experiences spasms and tremors. Despite his limitations, four-year-old Mark has managed to take his first steps and say a few words, but the most comforting thing is his smile when he sees his mother. Mark has been diagnosed with a neurodevelopmental delay of unknown origin, which worries Karol, as the lack of an accurate diagnosis makes it difficult to obtain support for the family. This situation, although fictitious, is common in many families who do not have a history of cognitive or neurodevelopmental disorders.
Challenges in the diagnosis of rare diseases
Despite advances in the genetic diagnosis of rare diseases, approximately 60% of patients with neurodevelopmental disorders or cognitive delay do not receive an accurate diagnosis, causing distress to parents who do not know the prognosis for their children or the likelihood that future children will also be affected. In the case of rare diseases of genetic origin, it is crucial to identify the name of the disease and the gene causing it in order to better understand the patient’s condition and plan treatment.
Advances in the identification of causative genes
Recently, two scientific articles have been published that have identified the gene causing many cases of cognitive delay associated with microcephaly and muscle hypotonia, as well as other distinctive facial symptoms. This discovery, presented at the European Congress of Human Genetics, has revealed the RNU4-2 gene as responsible for 0.41% of cases of cognitive delay, being the second most relevant gene after the MECP2 gene, associated with Rett syndrome. This finding raises the question about the delay in its identification, explained by the lack of searching in the appropriate location.
Implications and future research
This discovery marks the beginning of the search for new causative genes in the genome, especially in previously underestimated regions. Given the complexity of the human genome, which consists of 6.6 billion bases, there is a need to explore mutations in non-coding genes, antisense genes, regulatory regions, introns and other less studied areas. This renewed focus on genetic diagnosis of rare diseases promises to open new avenues to understand and address these conditions more effectively.