Category Archives: Research News & Updates

CdLS Researcher’s Work with Fruit Flies Creates Buzz


(From Saint Louis University’s web site)

Dorsett’s Work with Fruit Flies Creates Buzz: Biochemist Credits Lab Team Members for Dedication to Research

Dale Dorsett, Ph.D., a professor in the department of biochemistry and molecular biology, received an award for his research on a genetic syndrome from a national foundation.

The award recognizes an individual’s significant medical or scientific contributions toward understanding Cornelia de Lange Syndrome and improving the lives of those affected by it.

“The award really belongs to the people in my lab who have worked so hard over the past 10 years or so,” Dorsett said.

“It’s very exciting to be recognized for our work with fruit flies by a family organization dedicated to a human genetic syndrome. It definitely motivates us to do more. Virtually all scientists who work with fruit flies believe their work will eventually have direct implications for human health, but it’s uncommon for it to become so directly relevant within a few years of the initial discoveries.”

The second person to receive the recognition, Dorsett was chosen because his work with Drosophila (fruit flies) helps explain how and why Cornelia de Lange Syndrome happens. His work led to the identification of the NIPBL gene in Drosophila in 1999 and its role in development before it was discovered as the first Cornelia de Lange Syndrome gene in 2004.

Dorsett’s lab uses the molecular genetics and genomics of fruit flies to understand how chromosome structure controls gene expression during development. His lab’s work has shed light on the molecular mechanisms of Cornelia de Lange Syndrome, which causes multiple developmental delays in humans, including slow growth, intellectual disabilities and various structural birth defects.

Often unrecognized, Cornelia de Lange Syndrome is a genetic syndrome that occurs in about 1 in 10,000 births. An estimated 20,000 people in the U.S. have Cornelia de Lange Syndrome but remain undiagnosed and/or without support services.

Although individuals with Cornelia de Lange Syndrome range from mildly to severely affected, most have similar physical characteristics: small size, hands and feet; thin eyebrows that meet in the middle; long eyelashes; upturned nose; and thin, downturned lips.

Some individuals have problems with their limbs such as missing fingers or arms and partial joining of the toes. Common medical problems include gastroesophageal reflux, bowel obstruction, hearing loss and congenital heart defects.

Created in 2008, the award is inspired by the foundation’s former medical director, Laird Jackson, M.D., who began his involvement with the foundation more than three decades ago, and continues to remain active in research and clinical work.

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CdLS research (for the non-scientists among us)

If you want to know what fruit flies, zebrafish and mice have to do with helping people with CdLS, we’ve got just the place for you. Visitors to the CdLS Foundation web site can now view summaries of CdLS and CdLS-related research articles—written in layman’s terms, for the most part. This new Research Articles page is a meaningful connection to scientific research information that is relevant to our mission.

For copyright reasons, we cannot post entire articles. The summaries offer a glimpse of the article, as well as information about where to get the complete version, should one want to read it more depth.

More article summaries will be posted in the coming weeks (and in the future as they become available). Check it out today. –MM 

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And now, a word from one of our researchers …

Around the CdLS Foundation office, we err on the side of silliness when remembering names of genes and other scientific facts. You can’t expect too much from a group of social workers, some liberal arts majors and a part-time opera singer. For instance, when the second gene was found, no one could remember its name (SMC1A), so it became Start My Car. And then there’s sister chromatid cohesion. We like to picture two nuns holding our genes together.  

Obviously, it’s best we leave the scientific work to the experts, like Dr. Matthew Deardorff, a member of our Clinical Advisory Board and the research team at the Children’s Hospital of Philadelphia (CHOP). So, we thought we’d ask him to talk a little about the latest gene finding, and what it means. Read on below. –MM 

Recently, our group at CHOP in collaboration with a number of families and physicians from around the world were able to better understand the cause of CdLS in some patients by analyzing two additional genes, SMC1A and SMC3.  Last April, the SMC1A gene (a.k.a. SMC1L1) was discovered by our Italian colleagues, Drs. Antonio Musio and Angelo Selicorni.

Since we have the good fortune of having so many families participating in our research, we were able to test more than 100 individuals who did not show a change in NIPBL, the first gene found to cause CdLS (and found in more than 50 percent of affected individuals). We found SMC1A gene changes in 14 individuals, or about 5% of patients.  

It turns out that quite a bit of work has been done over the last 20 years to understand how SMC1A works—most of it in bacteria and yeast.  Follow-up work has shown that similar systems function in human cells also. Specifically, SMC1A and a number of other proteins are involved in one aspect of holding chromosomes pairs together (sister chromatid cohesion). We thought that maybe other genes that function in this process might also cause CdLS. So, we looked at a number of genes in about 100 patients and found a mutation in SMC1A’s partner, SMC3. 

When we looked carefully at the features of the patients with changes in these two genes, something was quite apparent:  all of these patients fit into a “milder” category of CdLS.  None had severe limb differences, and all had learned to walk and talk.  Even more notable was that as several of these individuals aged, the features that had enabled them to be diagnosed with CdLS as younger patients were much less apparent.

We have begun to wonder whether changes in these genes may cause not only mild CdLS, but may also be responsible for causing mental retardation in patients that we would not recognize as CdLS. While SMC1A and SMC3 may in the end prove to cause CdLS in only a small minority of patients, finding changes in these genes has clearly focused our attention on understanding how sister chromatid cohesion causes children to be born with CdLS. 

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