A mutation in the 5 ' non-high mobility group box region of the SRY gene in patients with Turner syndrome and Y mosaicism

In Ullrich-Turner syndrome (UTS) patients, the presence of a Y-chromosome o r Y-derived material has been documented in frequencies ranging from 4-61%. Mutations of SRY (testis-determining gene) constitute the cause of XY sex reversal in approximately 10-15% of females with pure gonadal dysgenesis. M ost of these mutations have been described in the HMG thigh mobility group) box of the gene, which is the region responsible for DNA binding and bendi ng; however, various mutations outside the HMG box have been reported. We c arried out molecular studies of the SRY gene in three patients with a UTS p henotype and bilateral streaks; two presented a 45,X/46,XY mosaic, and the third a Y marker chromosome. In two patients a missense mutation, S18N, was identified in the 5'non-HMG box region in DNA from blood and both streaks; this mutation was not identi fied in 75 normal males. Sequencing of the DNA region of interest was norma l in the father and older brother of patient 1, demonstrating that in this patient the mutation was de novo. A previous report of a 46,XY patient with partial gonadal dysgenesis who pr esented the same mutation as our patients indicates the probable existence of a hot spot in this region of the SRY gene and strengthens the possibilit y that; all gonadal dysgeneses constitute part of a spectrum of the same di sorder. It also demonstrates that a single genetic abnormality can result i n a wide range of phenotypic expression.