Rare syndrome causing intellectual disability identified

PHILADELPHIA, April 4 (UPI) -- Researchers in Philadelphia identified a genetic mutation causing a rare, specific type of intellectual disability in children, according to a new study.

The Children's Hospital of Philadelphia found in a DNA analysis that changes TBC1-domain-containing-kinase, or TBCK, causes the developmental disability in children, suggesting a genetic treatment may be possible for it at some point.

TBCK-related ID syndrome is caused by a recessive genetic mutation carried by both parents, causing developmental delays ranging from moderate to severe, low muscle tone and, in some children, seizures.

"This study may represent an early step toward the types of precision medicine treatment that may become more common as we draw on genomic research," Dr. Elizabeth Bhoj, a researcher at the Children's Hospital of Philadelphia, said in a press release.

For the study, published in the American Journal of Human Genetics, researchers analyzed DNA from 13 children of unrelated families, finding that while symptoms varied among the children, they all carried the genetic mutation. The parents of all the children, none of whom have the syndrome, also carry the gene.

The TBCK gene codes for a protein of the same name, which regulates signals along the mTOR pathway in cells. Abnormal signaling in this pathway is known to play a role in neurolobiological conditions, epilepsy, autism and other forms of intellectual disability.

The scientists found lower levels of the TBCK protein an slower mTOR signaling in the children's cells. When the amino acid leucine was added to cell cultures, mTOR signaling increased, suggesting it could be used to treat children with the syndrome.

"This work highlights how modern genetic approaches can uncover disease-causing variants in phenotypically heterogeneous samples that involve the same gene and molecular pathway," said Dr. Hakon Hakonarson, director of the Center for Applied Genomics. "Such molecular phenotyping can help clarify disease relationships and inform future treatments, in keeping with our precision medicine focus."