Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome wi th associated visceral and skeletal abnormalities. Alterations in the glypi can-3 gene (GPC3), which is located on Xq26, have been implicated in the et iology of relatively milder cases of this disorder. Not all individuals wit h SGBS have demonstrated disruptions of the GPC3 locus, which raises the po ssibility that other loci on the X chromosome could be responsible for some cases of this syndrome. We have previously described a large family with a severe form of SGBS that is characterized by multiple anomalies, hydrops f etalis, and death within the first 8 wk of life. Using 25 simple tandem-rep eat polymorphism markers spanning the X chromosome, we have localized the g ene for this disorder to an similar to 6-Mb region of Xp22, with a maximum LOD score of 3.31 and with LOD scores < - 2.0 for all of Xq. These results demonstrate that neither the GPC3 gene nor other genes on Xq26 are responsi ble for all cases of SGBS and that a second SGBS locus resides on Xp22.