Genetic profile reveals susceptibility to cleft palate

September 15, 2008

For the first time, researchers from the University of Pittsburgh School of Dental Medicine have identified a series of genetic mutations that appear to be linked to significant risk for cleft palate and other dental abnormalities. These are devastating conditions that cause tremendous social isolation, and also are associated with decreased lifespan, a higher risk of cancer and increased susceptibility to psychiatric disorders, even after surgical repair.

As reported in the September issue of Genetics in Medicine, Alexandre Vieira, DDS, Ph.D., assistant professor in the Department of Oral Biology, University of Pittsburgh School of Dental Medicine, and colleagues collected and evaluated genetic material from the saliva and blood of more than 500 individuals in family groups with two or more siblings affected with cleft lip or palate, and an additional 100 people from unrelated families whose samples were used for general-population comparison data. The researchers analyzed 1,489 variations in DNA sequences, known as single-nucleotide polymorphisms, in 150 genes.

"We found a group of more than a dozen gene mutations that appear to be significantly associated with cleft lip and palate, as well as other dental abnormalities – predominantly at the locations for ERBB2, CDH2 and IRF6," said Dr. Vieira, who is a pediatric dental specialist. "Here we report, for the first time, an extensive candidate gene analysis for cleft susceptibility, a crucial step that may allow for better estimates of recurrence risk in individual families."

Collecting the genetic data from members of extended family groups living among the 7,000 islands in the Philippines presented its own challenges in the form of typhoons and severe tropical storms, at least one major landslide and frequently thorny local political conditions that restricted areas to which researchers could safely travel. Field researchers were stranded for more than a week and pitched in to help emergency rescue personnel following a massive mudslide on Southern Leyte that caused widespread damage and loss of life in February 2006.

"In some cases, it would be two entire days of travel by boat, car and foot to reach just one family in a remote village,” said Dr. Vieira. “It took us about three years to finish the project."

The gene ERBB2 has been associated with aggressive breast cancer, while IRF6 is linked to formation of the connective tissue, such as the palate. CDH2 is a gene associated with left-right asymmetry. Other genes of interest that were identified include MSX1, PVR, PVRL and TGFA.

Associated tooth abnormalities studied included families where people had extra teeth, or teeth that were tiny or missing. Missing teeth was the most frequently observed abnormality, the researchers noted.

Cleft lip and palate is a common birth defect, on average affecting about one in 700 live births worldwide. In general, Asian populations have a higher prevalence of cleft lip and palate at about one in 500 births. Among Caucasians, the rate is one in 1,100, and African populations have the lowest rate at one in 2,500 births.

"In the Philippines, affected people can be completely isolated socially, miserable, alcoholic and heavy smokers with a hard time speaking. Access to care is very difficult," said Dr. Vieira. "The hope is to be able to narrow down the genes that cause clefts and to screen for that risk – and, eventually, to possibly lead to gene therapy targets, although that may not happen in my lifetime."

Source: University of Pittsburgh

Explore further: Smoking mothers more likely to have babies with dental abnormalities

Related Stories

Smoking mothers more likely to have babies with dental abnormalities

May 31, 2017
Women who smoke more than 10 cigarettes a day during pregnancy are much more likely to give birth to babies who will fail to grow all their teeth, new University of Otago research has found.

Epigenetics could help diagnose different types of cleft

June 15, 2017
Cleft lip and/or palate are common birth defects and affect around 15 in every 10,000 births in Europe. New research by the University of Bristol from the largest study of cleft lip and/or palate in the world, the Cleft Collective, ...

Experts make breakthrough in cleft lip and palate research

March 24, 2016
Leading scientists have identified an important gene that is associated with cleft lip and palate.

Researchers develop treatment to reduce rate of cleft palate relapse complication

September 22, 2017
Young people with cleft palate may one day face fewer painful surgeries and spend less time undergoing uncomfortable orthodontic treatments thanks to a new therapy developed by researchers from the UCLA School of Dentistry. ...

Understanding genetic synergy in cleft palate

July 19, 2017
Like all of the individual elements of fetal development, palate growth is a marvel of nature. In part of this process, ledges of tissue on the sides of the face grow downwards on each side of the tongue, then upward, fusing ...

Families of orofacial clefting not at higher risk for dental anomalies

June 16, 2015
Today, the International and American Associations for Dental Research (IADR/AADR) published a study titled "Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting," which is the largest international cohort to ...

Recommended for you

15 new genes identified that shape human faces

February 20, 2018
Researchers from KU Leuven (Belgium) and the universities of Pittsburgh, Stanford, and Penn State have identified 15 genes that determine facial features. The findings were published in Nature Genetics.

New software helps detect adaptive genetic mutations

February 20, 2018
Researchers from Brown University have developed a new method for sifting through genomic data in search of genetic variants that have helped populations adapt to their environments. The technique, dubbed SWIF(r), could be ...

New algorithm can pinpoint mutations favored by natural selection in large sections of the human genome

February 20, 2018
A team of scientists has developed an algorithm that can accurately pinpoint, in large regions of the human genome, mutations favored by natural selection. The finding provides deeper insight into how evolution works, and ...

Highly mutated protein in skin cancer plays central role in skin cell renewal

February 20, 2018
Approximately once a month, our skin completely renews itself. If this highly coordinated process goes awry, it can lead to a variety of skin diseases, ranging from skin cancer to psoriasis. Cells lining such organs as skin ...

Study of smoking and genetics illuminates complexities of blood pressure

February 15, 2018
Analyzing the genetics and smoking habits of more than half a million people has shed new light on the complexities of controlling blood pressure, according to a study led by researchers at Washington University School of ...

New mutation linked to ovarian cancer can be passed down through dad

February 15, 2018
A newly identified mutation, passed down through the X-chromosome, is linked to earlier onset of ovarian cancer in women and prostate cancer in father and sons. Kunle Odunsi, Kevin H. Eng and colleagues at Roswell Park Comprehensive ...


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.