title: A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Dentistry, Alkharj University, Alkharj, Kingdom of Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahid
authors.forename: Varinderpal S
authors.initials: VS
authors.lastname: Dhillon
authors.forename: Hesham Saleh
authors.initials: HS
authors.lastname: Khalil
authors.forename: Shameemul
authors.initials: S
authors.lastname: Haque
authors.forename: Swaraj
authors.initials: S
authors.lastname: Batra
authors.forename: Syed Akhtar
authors.initials: SA
authors.lastname: Husain
authors.forename: L H J
authors.initials: LH
authors.lastname: Looijenga
mesh_terms: D000328:Adult; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D010375:Pedigree; D051876:Sex-Determining Region Y Protein / Q000235:genetics*; D014424:Turner Syndrome / Q000235:genetics*
chemical_list: C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein