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International team discovers likely basis of birth defect causing premature skull closure in infants
Date:11/18/2012

s of craniosynostosis have previously been linked to a number of different genetic syndromes, but the vast majority of cases (not associated with a syndrome involving other birth defects) arise without any known family history or cause. The most common form of non-syndromic craniosynostosis ― affecting about 1 in 5,000 newborns ― involves the sagittal suture, the main seam that runs down the center of the top of the skull. These cases were the subject of the investigation.

Although the condition has long been thought to be partially determined by genes ― it is three times more common in boys than in girls, and identical twins are much more likely to both be affected than non-identical twins ― the exact basis was unclear.

To help determine the cause, the investigators conducted the first genome-wide association study for the disorder, which involves scanning the entire genome of a group of people with craniosynostosis and comparing it to a control group of people without the condition. The study searched for single nucleotide polymorphisms (abbreviated as SNPs and called "snips") that are associated with craniosynostosis. SNPs are DNA changes in which a single nucleotide differs from the usual one at that position. There are some three billion nucleotides, the basic building blocks of DNA, in the human genome.

The study first evaluated the DNA ― extracted from whole blood or oral samples ― of 214 children and both of their parents, who did not have the condition, and restricted their final analysis to a group of 130 non-Hispanic white child-parent trios. This approach reduces the genetic variability inherent to individuals from different ethnicities. Their results identified very strong associations to SNPs in two areas of the genome, coding for bone morphogenetic protein 2 (BMP2) and Bardet-Biedl syndrome 9 protein (BBS9). Both proteins are known to play a role in skeletal development.

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Contact: Phyllis Brown
phyllis.brown@ucdmc.ucdavis.edu
916-734-9023
University of California - Davis Health System
Source:Eurekalert

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