Researchers have made one less condition unclassified after they correctly identified a new genetic neurological disorder using DNA sequencing. This technique is different to the traditional method that doctors have used to define diseases, which involves diagnosis based on patient symptoms or clinical features. The discovery represents a transformation in the way that medicine is practiced and could also help to shed some light on how to better treat already existing neurological conditions.
The genetic brain disorder was identified through the collaboration of two independent scientific teams. The two studies can be found in the science journal, Cell. Separately, the teams performed DNA sequencing on more than 4,000 families that were affected by a neurological problem. They discovered that each child affected by the undiagnosed neurological problem was carrying a mutation in the CLP1 gene. Each child also displayed similar symptoms of brain malformations, intellectual disabilities, seizures, and sensory and motor defects.
Once the teams had spotted the gene in seven of the families, they could see that it was a common feature. “Identification of yet another genetic cause for this neurodegenerative disorder will allow for better genetic testing and counseling to families with an affected child,” Frank Bass, a member of the research team from the Academic Medical Center in the Netherlands, said in a press release.
The mutation is in a gene called CLP1. The CLP1 protein is known to regulate tRNA metabolism in cells. It is also important in generating mature, functional molecules called RNAs (tRNAs). RNAs transport amino acids to cellular subunits called ribosomes for assembly into proteins. Mutations in molecules involved with RNAs have already been associated with human neurological disorder, such as pontocerebellar hypoplasia (PCH), a neurodegenerative disease that affects children.
This is the first time, however, that scientists have realized the specific role that CLP1 plays in human disease. This newly identified genetic condition is believed to be a new form of PCH. It should be noted that last year Josesph G. Gleeson, a led researcher of the study, and his colleagues, published a paper that identified a different gene mutation for a particularly severe form of PCH, and reported evidence that a nutritional supplement might one day be able to prevent or reverse the condition.
The study of this particularly rare condition is likely to affect the future treatment of many different neurological conditions. “Knowing fundamental pathways that regulate the degeneration of neurons should allow us to define new pathways that when modulated might help us to protect motor neurons from dying, such as in Lou Gehrig’s disease, Josef Penniger, one of the study's researchers from the Austrian Academy of Sciences, explained in the press release.
Pontecerebellar hypoplasia is characterized by incoordination of sucking and swallowing, impaired motor and cognitive development with lack of voluntary motor development, central visual impairment, and an increased risk for malignant hyperthermia. Epilepsy is also common in children with PCH. Although it can be managed, there is currently no cure for the condition.