Analysis of the SRY gene in two sex-reversed XY sisters identifies two new novel point mutations in the high mobility group box domain.
OBJECTIVE
To determine mutations in the SRY gene in two sisters with 46, XY karyotype.


METHODS
Case report.


METHODS
Jamia Millia Islamia, New Delhi, and CSIRO Human Nutrition, Adelaide, Australia.


METHODS
Two sisters aged 23 and 27 years old with primary amenorrhea.


METHODS
Endocrine, mutations in the SRY gene, and DNA binding ability.


METHODS
LH, FSH, and testosterone levels, DNA sequence findings.


RESULTS
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.


CONCLUSIONS
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.
Shahid
Mohd
M
Department of Biosciences, Human Genetics Lab, Jamia Millia Islamia, A Central University, Jamia Nagar, New Delhi, India. shahid_qureshi2000@yahoo.com
Dhillon
Varinderpal S
VS
Hussain
Zahid
Z
Masa
Juan F
JF
Aslam
Mohd
M
Raish
Mohd
M
Ahmad
Arif
A
Khan
Nida Jamil
NJ
Prasad
Sudha
S
Batra
Swaraj
S
Pasha
Syed T
ST
Husain
Syed Akhtar
SA
D000328:Adult; D012734:Disorders of Sex Development; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics*; D024742:HMG-Box Domains / Q000235:genetics*; D006801:Humans; D017354:Point Mutation; D051876:Sex-Determining Region Y Protein / Q000235:genetics*; D035781:Siblings
C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein