Gene discovered for Weaver syndrome

December 15, 2011

Scientists have found a gene that causes Weaver syndrome, a rare genetic disorder that typically causes large size at birth, tall stature, developmental delay during childhood, and intellectual disability. Published today in the American Journal of Human Genetics, the discovery means that testing the EZH2 gene for mutations could help families who are seeking a diagnosis for their child.

"For the families among whom we identified the gene, this discovery definitively brings the diagnostic odyssey to a close – it's DNA confirmation that their children have Weaver syndrome," says Dr. William Gibson, the study's lead investigator. Dr. Gibson is a clinician scientist at the Child & Family Research Institute at BC Children's Hospital and an assistant professor in the Department of Medical Genetics at the University of British Columbia (UBC).

"Our discovery enables DNA-based diagnostic testing for this particular disease," says Dr. Gibson. "For physicians who suspect Weaver syndrome in one of their patients, we can now confirm it if we find in EZH2. There may still be other Weaver syndrome , and we need to study more families to be sure."

Presently, doctors diagnose Weaver syndrome by assessing a child's face, growth, skeleton and other clinical features. People with Weaver syndrome have an oversized head, typical facial features, problems with muscle tone and joints, and differences in the way their skeleton matures. Mutations in the NSD1 gene, which normally causes a rare disease called Sotos syndrome, are also known to cause Weaver syndrome in some cases. There may be other genes involved in Weaver syndrome that are yet to be discovered.

"Now we have an answer for these families and we are also in a position to provide answers to other families affected by this rare and difficult disease," says Dr. Gibson. He is available to see new patients clinically for of Weaver syndrome. As a result of this discovery, Dr. Gibson's team now offers sequencing of the EZH2 gene on a research basis in partnership with the Ottawa Hospital Research Institute. Dr. Gibson's team can be contacted by email at wtgibson@cfri.ubc.ca.

Traditionally, hunting for a disease-causing gene has relied on tracking a gene throughout a family's history. However, Weaver syndrome usually occurs only once in a family, as it is thought to be caused by a new genetic mutation in the sperm or egg that conceived the child. For this study, the investigators sought patients with Weaver syndrome from Canada and the United States. They approached Dr. David Weaver, who discovered the syndrome in 1974 and is professor emeritus of Medical and Molecular Genetics at Indiana University School of Medicine in Indianapolis. In two families that Dr. Weaver had examined, the Canadian team looked for brand new genetic mutations by comparing the DNA of affected children to DNA from their unaffected parents. Once the investigators identified EZH2 as a candidate gene, they sequenced it in DNA samples from a third Canadian family. They confirmed that an EZH2 mutation was in this third family's child but not in either of her healthy parents.

EZH2 is a cancer gene that is known to be mutated in leukemia, B-cell lymphomas and some other blood cancers. The gene helps control how DNA is packaged around specific proteins, which in turn helps to regulate which groups of genes are turned off and on.

"Our finding illuminates an emerging area of biology that links developmental syndromes and cancer," says Dr. Gibson. "It appears that some mutations in EZH2, if these occur early in life, produce developmental syndromes such as Weaver syndrome, whereas mutations in the same gene that occur later in life can produce cancer."

Dr. Steven Jones is the study's senior author who led the DNA sequencing and bioinformatics. He is head of bioinformatics and associate director of the Michael Smith Genome Sciences Centre at BC Cancer Agency, professor in the UBC Department of Medical Genetics, and professor, Molecular Biology & Biochemistry at Simon Fraser University (SFU).

Explore further: Researchers discover hereditary predisposition of melanoma of the eye

Related Stories

Researchers discover hereditary predisposition of melanoma of the eye

December 15, 2011
Ohio State University researchers have discovered a hereditary cancer syndrome that predisposes certain people to a melanoma of the eye, along with lung cancer, brain cancer and possibly other types of cancer.

Recommended for you

New clues to treat Alagille syndrome from zebrafish

October 18, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies potential new therapeutic avenues for patients with Alagille syndrome. The discovery, published in Nature Communications, ...

Genetic variants associated with obsessive-compulsive disorder identified

October 18, 2017
(Medical Xpress)—An international team of researchers has found evidence of four genes that can be linked to obsessive-compulsive disorder (OCD). In their paper published in the journal Nature Communications, the group ...

An architect gene is involved in the assimilation of breast milk

October 17, 2017
A family of "architect" genes called Hox coordinates the formation of organs and limbs during embryonic life. Geneticists from the University of Geneva (UNIGE) and the Swiss Federal Institute of Technology in Lausanne (EPFL), ...

Study identifies genes responsible for diversity of human skin colors

October 12, 2017
Human populations feature a broad palette of skin tones. But until now, few genes have been shown to contribute to normal variation in skin color, and these had primarily been discovered through studies of European populations.

Genes critical for hearing identified

October 12, 2017
Fifty-two previously unidentified genes that are critical for hearing have been found by testing over 3,000 mouse genes. The newly discovered genes will provide insights into the causes of hearing loss in humans, say scientists ...

Team completes atlas of human DNA differences that influence gene expression

October 11, 2017
Researchers funded by the National Institutes of Health (NIH) have completed a detailed atlas documenting the stretches of human DNA that influence gene expression - a key way in which a person's genome gives rise to an observable ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.