A NEW DE-NOVO MUTATION (A113T) IN HMG BOX OF THE SRY GENE LEADS TO XYGONADAL-DYSGENESIS

We describe a new point mutation in the SRY gene of a Chinese XY femal e with gonadal dysgenesis (Swyer syndrome). Using the double stranded DNA cycle sequencing method, a single nucleotide substitution of G-->A was identified at codon 113 of the patient's SRY gene, resulting in a conservative amino acid change from alanine (A) to threonine (T) at a residue that lies within the putative DNA binding motif. With this mu tation, one Mn1I recognition site is abolished and a new BsmAI site is present in the DNA sequence of the SRY gene; therefore, it is easily detected by analysis of the digestion of the amplified SRY DNA fragmen t on an electrophoretic agarose gel. In situ hybridisation to the XY f emale's chromosomes showed that her mutant SRY gene was indeed located on the short arm of her Y chromosome. The SRY mutation in the XY fema le reported here occurred de novo, as sequence analysis showed that it was not present in her father or other family members.