title: Analysis of the SRY gene in two sex-reversed XY sisters identifies two new novel point mutations in the high mobility group box domain.
abstract: 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.
authors.affiliation: Department of Biosciences, Human Genetics Lab, Jamia Millia Islamia, A Central University, Jamia Nagar, New Delhi, India. shahid_qureshi2000@yahoo.com
authors.forename: Mohd
authors.initials: M
authors.lastname: Shahid
authors.forename: Varinderpal S
authors.initials: VS
authors.lastname: Dhillon
authors.forename: Zahid
authors.initials: Z
authors.lastname: Hussain
authors.forename: Juan F
authors.initials: JF
authors.lastname: Masa
authors.forename: Mohd
authors.initials: M
authors.lastname: Aslam
authors.forename: Mohd
authors.initials: M
authors.lastname: Raish
authors.forename: Arif
authors.initials: A
authors.lastname: Ahmad
authors.forename: Nida Jamil
authors.initials: NJ
authors.lastname: Khan
authors.forename: Sudha
authors.initials: S
authors.lastname: Prasad
authors.forename: Swaraj
authors.initials: S
authors.lastname: Batra
authors.forename: Syed T
authors.initials: ST
authors.lastname: Pasha
authors.forename: Syed Akhtar
authors.initials: SA
authors.lastname: Husain
mesh_terms: 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
chemical_list: C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein