A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient

Journal Article

Looijenga6, Mohammad Shahid1,3, Varinderpal S Dhillon2*, Hesham Saleh Khalil3, Shameemul Haque4, Swaraj Batra5, Syed Akhtar Husain4, LHJ . 2010

Publication Abstract

Background: Sex determining factor (SRY) located on the short arm of the Y chromosome, plays an important role
in initiating male sex determination, resulting in development of testicular tissue. Presence of the SRY gene in
females results in XY sex reversal and increased risk of gonadal germ cell tumours if the karyotype also includes
the so-called GonadoBlastoma on the Y chromosome (GBY) region. The majority of mutations within the SRY gene
are de novo affecting only a single individual in the family. The mutations within the high-mobility group (HMG)
region have the potential to affect its DNA binding activity.
Case Presentation: We performed G- and R-banding cytogenetic analysis of the patient and her family members
including her father. We also performed molecular genetic analysis of SRY gene. Cytogenetic analysis in the patient
(Turner Syndrome) revealed the mosaic karyotype as 45, X/46, XY (79%/21% respectively) while her father (milder
features with testicular dysgenesis syndrome) has a normal male karyotype (46, XY). Using molecular approach, we
screened the patient and her father for mutations in the SRY gene. Both patient and her father showed the same
deletion of cytosine within HMG box resulting in frame shift mutation (L94fsX180), the father in a mosaic pattern.
Histological examination of the gonads from the patient revealed the presence of gonadoblastoma formation,
while the father presented with oligoasthenozoospermia and a testicular seminoma. The frameshift mutation at
this codon is novel, and may result in a mutated SRY protein.
Conclusion: Our results suggest that lack of a second sex chromosome in majority cells of the patient may have
triggered the short stature and primary infertility, and the mutated SRY protein may be associated with the
development of gonadoblastoma. It is of importance to note that mosaic patients without a SRY mutation also
have a risk for malignant germ cell tumors.