Understanding Genetic Testing Results
There are different ways changes in our genes might cause SATB2-associated syndrome (SAS). These include: contiguous large deletions (missing pieces that include SATB2 as well as other genes nearby), intragenic deletions (missing pieces of just SATB2), large duplications (extra pieces that include SATB2 as well as other genes), intragenic duplications (extra pieces of just SATB2), translocations (chromosome abnormality caused by rearrangement of parts between chromosomes) that include SATB2, and mutations (misspellings). We encourage you to read the Background Information section first, so that some of the terms used can be easily understood.
Contiguous large deletions
Deletions (missing pieces) of several genes are labeled contiguous. This is the most commonly reported change involving the SATB2 gene. Chromosome 2 is the second largest human chromosome spanning about 243 million building blocks of DNA (base pairs). Contiguous large deletions are typically found through a test called a microarray (also known as array CGH or SNP array). The reports are usually written similarly: arr [hg19] 2q33.1 (198,356,789-203,491,035)x1. In this particular example, first we can tell there is a deletion by the “x1” at the end that indicates that only one copy is present instead of the normal two (one from mom and one from dad). Then, the “2q33.1” refers to the location where the deletion is. Lastly, the numbers indicate with more precision what exactly is missing, a bit like GPS coordinates. In this case, approximately 5 million letters are missing, abbreviated 5 Mb. One copy of the SATB2 gene, located in chromosome 2 at position q33.1 around the 200,000,000 position is therefore expected to be missing because the letters located between 198 million and 203 million are missing. Microarray tests from many years ago may have slightly different numbers that still correspond to the same genes. This is because over the years, as we learn more about DNA, we have to adjust the count of base pairs.
Deletions (missing pieces) that only include a part of the SATB2 gene are labeled intragenic. Intragenic deletions have only been reported in a handful of patients. An example of an intragenic deletion report from a patient in Dr. Zarate’s study is: arr [hg19] 2q33.1(200,180,939-200,200,560)x1. In this particular example only 2 exons (coding regions of the gene) out of the normal 11, are missing. Because the exons are critical in providing the correct information to form the protein, the SATB2 gene copy that has that piece missing is unlikely to work properly.
Contiguous large duplications
Duplications (extra pieces) of multiple genes that include SATB2 have rarely been reported. It is unclear if having this extra piece results in similar signs and symptoms for patients compared to the other mechanisms listed.
Duplications (extra pieces) that only include a part of the SATB2 gene are labeled intragenic. Intragenic duplications have only been reported in a handful of patients. An example of an intragenic duplication report from the literature is: arr [hg19] 2q33.1 (200,256,583-200,340,204) x3 (Kaiser et al.). In this particular example the duplication is indicated by the “x3” at the end which means that there are 3 copies of that area instead of the usual two. Only 1 exon (coding regions of the gene) out of the normal 11 is extra in this case. Because the exons are critical in providing the correct information to form the protein, the SATB2 gene copy that has that extra piece is unlikely to work properly.
Sometimes one chromosome may be attached to another chromosome improperly and be rearranged. This is called a chromosome translocation, and can be a perfectly normal finding or can cause signs and symptoms. Rearrangements between chromosome 2q33.1 and other chromosomes have rarely been reported. If the rearrangement breaks are located within the SATB2 it could also “break” the gene and make it not work properly.
Mutations inside the gene
Mutations (Misspellings) of the SATB2 gene have been reported in a several patients making this the second most frequent cause of SAS. There are different types of mutations, also called pathogenic variants. Some examples from patients enrolled in Dr. Zarate’s study are provided below: