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Fertil Steril. 2008 Oct;90(4):1199.e1-8. doi: 10.1016/j.fertnstert.2007.11.062. Epub 2008 Mar 4.

Analysis of the SRY gene in two sex-reversed XY sisters identifies two new novel point mutations in the high mobility group box domain.

Author information

  • 1Department of Biosciences, Human Genetics Lab, Jamia Millia Islamia, A Central University, Jamia Nagar, New Delhi, India. shahid_qureshi2000@yahoo.com

Abstract

OBJECTIVE:

To determine mutations in the SRY gene in two sisters with 46, XY karyotype.

DESIGN:

Case report.

SETTING:

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

PATIENT(S):

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

INTERVENTION(S):

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

MAIN OUTCOME MEASURE(S):

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

RESULT(S):

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.

CONCLUSION(S):

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.

PMID:
18304538
[PubMed - indexed for MEDLINE]
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