A newly identified genetic disorder associated with degeneration of the central and peripheral nervous systems in humans, and its genetic cause, has been reported in the journal Cell. By performing DNA sequencing of more than 4,000 families affected by neurological problems, researchers discovered that a disease marked by reduced brain size and sensory and motor defects is caused by a mutation in a gene called CLP1, which is known to regulate tRNA metabolism in cells. The findings were generated by two independent but collaborative research teams based in the Unites States and the Netherlands.
Each child tested was affected by undiagnosed neurological problems. All of the children were discovered to carry a mutation in the CLP1 gene and displayed the same symptoms, such as brain malformations, intellectual disabilities, seizures, and sensory and motor defects. Seven out of the more than 4,000 families studied shared an identical CLP1 mutation.
The CLP1 protein plays an important role in generating mature, functional molecules called transfer RNAs (tRNAs), which shuttle amino acids to cellular subunits called ribosomes for assembly into proteins. Mutations affecting molecules involved in producing tRNAs have been implicated in human neurological disorders, such as pontocerebellar hypoplasia (PCH), a currently incurable neurodegenerative disease affecting children. Although CLP1 mutations have been linked to neuronal death and motor defects in mice, the role of CLP1 in human disease was not known until now.
“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,” says Josef Penninger, MD, a member of one of the research teams. Read the article.
Read more
