We describe a novel mutation in the coding region of theSRY gene in a 46, XY female with Swyer syndrome. Analysis ofSRY was carried out by direct sequencing of a 780-bp PCR product that included theSRY open reading frame (ORF). This revealed the presence of a point mutation, ins 108A, in the coding region 5’ to the HMG box which results in a frame shift and premature termination of the encoded protein. No other mutation was found in theSRY ORF. We infer that sex reversal in this individual is a result of this insertion. In none of the 13 other 46, XY females that were studied was a mutation detected inSRY, confirming earlier findings that most cases of XY femaleness are due to causes other than mutation inSRY. These observations and those of others are discussed in relation to the aetiology of XY sex reversal.

During a study of deletions of Y-chromosomal DNA in infertile males, sY116, a Y-linked STS, showed different electrophoretic mobilities in three males, two infertile and one fertile. A study of this STS among 35 other normal males showed that this locus is polymorphic. sY1 16 has a polyA-rich stretch whose instability appears to be the most likely cause of this polymorphism. The possible usefulness of sY116 polymorphism in the detection of subtle genome-wide instabilities in some types of cancer is discussed.