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Gene linked to both cleft lip, palate

U. IOWA (US)—An international research team has identified a gene that plays a major role in cleft lip and cleft palate. The findings could improve genetic counseling and potentially lead to improved treatment for the birth defect.

Details of the work led by researchers from the University of Iowa were published recently in the journal Human Molecular Genetics.

Previous work by the Iowa team had identified a segment of the human genome called chromosome 9 as the location of an important genetic cause of cleft lip and palate. Through further analysis of DNA from affected families, the researchers have now identified a single gene on that chromosome as a root cause of these common birth defects that affect between one in 500 and one in 1,000 births worldwide. In Iowa, the occurrence is one in 650 births.

The gene, known as FOXE1, appears to contribute to cleft lip with or without cleft palate and to isolated cleft palate. Previously, these two forms of clefting were thought to arise from different genetic abnormalities.

“For us to find that this one gene actually is involved in both types of clefting is interesting because it suggests that this gene is involved very early in the development of both the lip and palate,” says Lina Moreno, assistant professor in the orthodontics department at the UI College of Dentistry, who co-led the study with Adela Mansilla, a postdoctoral researcher in pediatrics at the UI Carver College of Medicine.

“In normal development, the lips form during the seventh week of pregnancy and then the palate forms by week 12. Our study suggests this gene is required for lip formation early on and then again, later, for palate formation,” Moreno adds.

Although the study suggests that FOXE1 abnormalities contribute to cleft lip and cleft palate, the researchers have not yet found the exact mutation in the gene that causes clefting. Instead, they have identified a variation in the genetic code that acts as a marker for the mutation.

The variation appears to “travel” with the mutation that causes cleft lip and palate when the gene is inherited, and the study suggests that the presence of the variant contributes to approximately 20 percent of all clefts. The team found the variant in affected families from the United States, the Philippines, Columbia, and Europe.

“The genetic finding was true across patient populations from around the world, which suggests it is a true finding and contributes risk for every population,” Moreno says. “Once we find the actual mutation within this gene that causes cleft lip and palate, we can better estimate people’s risk of having a cleft. So it has implications for genetic counseling.”

Genetic testing and counseling can help families prepare for the possibility that their child might be born with a cleft. For example, a family might choose to have their baby at a hospital capable of providing the multidisciplinary care needed to treat cleft lip or palate.

Although researchers do not yet know how FOXE1 abnormalities cause clefting, the gene might be part of a new pathway involved in lip and palate formation. In addition, FOXE1 is known to have a role in formation of the thyroid gland, which might mean there is a connection between thyroid function and cleft lip and palate.

Understanding what the mutation does to the gene and which biological pathways are affected could potentially lead to new therapeutic approaches.

The research team also included scientists from the University of Pittsburgh; University of Antioquia in Medellin, Columbia; University of Washington in Seattle; Children’s Hospital Oakland Research Institute in Oakland, Calif.; University of Southern Denmark; University of Bergen in Norway; Royal Children’s Hospital in Melbourne, Australia; the National Institutes of Health; and Johns Hopkins University.

The study was funded in part by grants from the March of Dimes, the National Institutes of Health, the Cleft Palate Foundation, and the American Association of Orthodontics Foundation.

University of Iowa news: http://news.uiowa.edu/

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9 Comments

  1. Lsmith

    Very interesting post. I’m glad to see medical professionals are continual trying to better understand cleft lips and palates. Identifying a gene that plays a major role in this condition is definitely a step in the right direction. Anything that can help improve genetic counseling and treatment is a great accomplishment.

  2. undiesinabunch

    Genetic counseling seems to be meaningless to many born with these birth defects. YouTube displays multitudes of videos by people with cleft palate and cleft lip who think nothing of producing offspring who might bear the mark of their disfigurement. But if you read the YouTube comments by the recipients of this mutation most feel severely impacted by it including myself.

  3. Lana

    I really like this post. Identifying an essential gene for cleft lip is a huge step and I am so glad the research for this unfortunate defect continuing!

  4. Laura

    Surgeries for many young children are need. <a href= http://hubpages.com/hub/The-Smile-Train-Helping-Children-With-Cleft-Lips smile train Check out Smile Train to learn how and why they fix cleft palate issues for free!

  5. Lauren

    Nice to see that there are people out there searching for cures about the children most people often forget. smile train cleft lip cleft palate is one such organization that cares for these children!

  6. Holly

    Since left lip/palate occurs with such frequency, the cost of correcting this anomaly so high and insurance coverage SO poor, I’m thrilled that there is research being done! I am the mother of a child with CL/CP and have fought for decades to find experienced, qualified doctors and competent insurance companies It is sad that the general public thinks that just closing the lip and/or the palate is enough. Years and years of orthodontics, ENTs, speech, dentistry and counseling are required for these children. Insurance coverage is out there. Don’t use any dental insurance…fight for medical coverage. This is a birth defect, it is NOT cosmetic or dental in nature. Please continue to contribute to any university who is doing research!

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