Abstract
To determine mutations in the SRY gene in two sisters with 46, XY karyotype.
Case report.
Jamia Millia Islamia, New Delhi, and CSIRO Human Nutrition, Adelaide, Australia.
Two sisters aged 23 and 27 years old with primary amenorrhea.
Endocrine, mutations in the SRY gene, and DNA binding ability.
LH, FSH, and testosterone levels, DNA sequence findings.
We found a new point mutation in the SRY gene in patient 1 at position +275 (A>T), which results in amino acid change (K92M). In patient 2, we found a double mutation in the SRY gene at two different loci. The first mutation is a substitution of C at +352, resulting in a change of amino acid (A118P), and second is deletion of T, resulting in a frame shift within a highly conserved DNA-binding motif-high mobility group box at +379 (T127IfsX179). Electrophoretic mobility shift assay showed that mutant K92M and A118P show reduced and greatly reduced binding ability, respectively. These mutations have the potential to interfere with protein–DNA binding activity and nuclear localization necessary for interactions of these proteins with DNA.
Our results suggest involvement of the SRY gene in sex reversal, which supports the relationship between SRY alterations, gonadal dysgenesis, and/or primary infertility, and provides further evidence of a high-mobility group box significance in DNA-binding/-bending properties.