Researchers identify causative gene for features of 2q32q33 microdeletion syndrome

Researchers at Signature Genomic Laboratories, which performs diagnostic genetic testing of chromosome abnormalities in individuals with unexplained mental retardation and/or birth defects, recently identified what is likely to be the causative gene for features of 2q32q33 microdeletion syndrome.

Individuals with the syndrome, which is caused by the loss of a small portion of DNA near the end of the long arm of chromosome 2, have severe mental retardation, growth retardation, unusual facial features, thin and sparse hair, feeding difficulties and cleft or high palate. Although deletions of varying amounts of DNA have been reported, the smallest region deleted in all patients contains at least seven genes. One of these genes, SATB2, is a DNA-binding protein that regulates how genes are expressed. The presence of only one copy of SATB2, which occurs when one of the two copies normally present in humans has been deleted or mutated, has been suggested to cause the cleft or high palate of individuals with 2q32q33 microdeletion syndrome. In their study, the results of which were published online in the journal PloS ONE, researchers at Signature identified three individuals with small deletions of this region, all of which spanned part of SATB2. After enrolling the patients in a study, review of clinical records showed similar clinical features among these individuals, including severe developmental delay, behavioral problems and tooth abnormalities. Interestingly, only one of the individuals had a cleft palate. Because the individuals had a portion of only one gene missing and the presence of many of the features associated with the larger microdeletion syndrome, the study authors suggested deletion of SATB2 was sufficient to cause several of the clinical features associated with 2q32q33 microdeletion syndrome.

“These results are exciting because they demonstrate microarray analysis can help identify the cause of some clinical features associated with genetic disorders. Identifying the causative gene, in some cases, may lead to treatment targets in the future,” said Dr. Lisa G. Shaffer, Ph.D., President and CEO of Signature and senior author of the study. “These results are particularly important for syndromes that have only been identified in a small number of individuals, because they allow us to define the clinical spectrum of the syndrome better.”

Added Dr. Shaffer, “the identification of such small abnormalities in these patients also demonstrates that, for diagnostic purposes, it is imprudent to assume that DNA gains and losses under a certain size are not clinically relevant to the patient’s features. Some laboratories use an arbitrary cutoff for alteration sizes to decide clinical relevance. We have many examples in GCAD, our proprietary database of alterations identified at our laboratory, of small alterations we deemed clinically relevant after comparison to other cases in the database and scientific literature. GCAD was developed after testing more than 40,000 patients and contains over 8,000 diagnoses. We are committed to publishing unique cases to aid other laboratories in the use of microarrays.”

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