Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

Original research article by R. Acuna-Hidalgo et al. (2017).

Read the abstract here.

Researchers have not yet been able to identify the specific function of the SETBP1 gene in the body; however, studies have suggested a link between genetic changes (mutations) in specific areas of the gene and certain features. One rare syndrome associated with changes in the SETBP1 gene is called Schinzel-Giedion syndrome (SGS). SGS is a rare disorder, associated with developmental delay, differences in facial and skeletal features, small head size (microcephaly), and in some cases, blood cancers. SGS is associated with a very specific part of the SETBP1 gene, which the authors of this article refer to as the “SETBP1 hotspot.” Mutations in this hotspot, are referred to as “gain of function,” meaning that they cause the gene to function with increased activity. It should be noted that these gain of function mutations are very specifically linked to SGS, and are not the same at the mutations observed in many of our Simons VIP families (like the mutations detailed in the Coe et al. research article). The mutations observed in the Simons VIP population are typically considered “loss of function” mutations, which are not known to be associated with any increased cancer risk.