SEP 10, 2016 08:25 AM PDT

Rare Skull Fusion Disorder Caused By Gene Variant

WRITTEN BY: Kara Marker
When the bones of an infant’s skull fuse too early, the growing brain is dangerously confined to a small space, causing various deformities of the facial and skull bones in addition to cognitive malfunction. In a new study from Rockefeller University, scientists have identified two rare mutations that cause the disease, called craniosynostosis, and the unique series of events that precede them.
Credit: The Rockefeller University/eLife
Nearly 200 families were recruited to participate in the study, which focused on identifying mutations causing a specific type of craniosynostosis, called midline or sagittal craniosynostosis. Signs of the disease occur quickly after birth, with an oblong shape of the head being a major indicator.

Researchers conducted multiple genetic tests to investigate the pattern of inheritance for disease-causing gene mutations. After sequencing the participants’ exomes, the part of the genome that contains the protein-coding genes, they connected mutations in a gene called SMAD6 to children with craniosynostosis. However, none of the parents of children with the disease shared the condition, even if they also had the SMAD6 mutation. 

SMAD6 inhibits BMP signaling, a processes that promotes bone formation. The SMAD6 mutation in the children with craniosynostosis prevented proper inhibition of bone formation in the skull, leading to early skull fusion. However, since other participants with the same SMAD6 mutation were perfectly healthy, the researchers knew there had to be another part of the genetic equation that they were missing. 

The next suspect was a gene called BMP2, which is connected to the same bone formation pathway as SMAD6. They found that the same children from the study who had the SMAD6 mutation and craniosynostosis also had a mutation in BMP2. Without SMAD6, these children were already missing a key piece of the puzzle for bone formation. The BMP2 mutation only further worsened the condition of premature bone formation and fusion. 

It appears that both BMP2 and SMAD6 mutations are needed to cause midline craniosynostosis. Confirming the relationship will help families and doctors decide the risk of disease. 

“In each case, the SMAD6 mutation came from one parent and the BMP2 risk variant came from the other parent, explaining why neither parent had craniosynostosis," said first author of the study, Andrew Timberlake.

Scientists believe their research might also apply to other rare genetic diseases, potentially answering lead author Richard P. Lifton’s question: “Why do some individuals with potent rare mutations develop disease, while others with the same mutations do not?"

Lifton’s study was recently published in the journal eLife.
 


Sources: Rockefeller University, Johns Hopkins Medicine
 
About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
SEP 05, 2018
Videos
SEP 05, 2018
Mosquitoes' Attraction to You May be Genetic
Are you a person that seems always to get bitten by mosquitoes?...
SEP 17, 2018
Cell & Molecular Biology
SEP 17, 2018
A Fast New Method to Make an Important Type of Brain Cell
Scientists have developed a better way to create astrocytes, a cell type hat has been implicated in neurodegenerative diseases....
SEP 19, 2018
Genetics & Genomics
SEP 19, 2018
Forensic Efforts To Combat Ivory Poaching
Scientists are using DNA testing to identify poaching hotspots, and criminal networks....
OCT 01, 2018
Genetics & Genomics
OCT 01, 2018
Digging Into the Details of DNA Replication
Cells have to carry around a huge amount of genetic material, and usually that DNA is about 1000 times longer than the cell where it lives....
NOV 01, 2018
Genetics & Genomics
NOV 01, 2018
Genetic Risk Factor for Erectile Dysfunction is Discovered
Scientists have discovered a gene that is connected to erectile dysfunction for the first time. This work may help improve therapeutics for the problem....
NOV 10, 2018
Videos
NOV 10, 2018
Engineering Viable Offspring From Same-sex Mouse Parents
Using a special kind of stem cell and genetic engineering, researchers have learned more about what's possible in reproduction....
Loading Comments...