SRY (sex-determining region Y) gene, MIM 480000, NM_005634) is crucial for sex differentiation which encodes the protein responsible for initiating testis differentiation. SRY mutations are associated with the presence of XY gonadal dysgenesis symptoms. We studied a 46,XY female patient with primary amenorrhoea and negative family history. The clinical, endocrine, histopathologic and cytogenetic data are consistent with gonadal dysgenesis. Using a molecular analysis, a novel (c.341A>G, p. N65D) missense mutation within the HMGbox of SRY gene was detected. Escherichia coli expression of SRY study showed reduced expression of the mutated protein and gel retardation assay method revealed lowered DNA-binding ability in N65D variant of SRY. The novel mutation detected in the SRY gene may be an aetiopathogenic factor in clinically defined 46,XY complete gonadal dysgenesis (CGD). Because of an increased risk of gonadoblastoma, proper early diagnosis and treatment prevent development of malignancies.
Keywords: CGD; Complete Gonadal Dysgenesis; DSD; Disorder of Sex Development; Disorder of sex development; HMG; HMG-box; High Mobility Group; Missense mutation; NLS; NR5A1; NROB1; Nuclear Localization Signal; R-spondin 1; RSPO1; SOX9; SRY; SRY (sex determining region Y)-box 9; SRY gene; Sex-determining Region of Y chromosome; WNT4; WT1; Wilms tumor 1; nuclear receptor subfamily 0, group B, member 1; nuclear receptor subfamily 5, group A, member 1; wingless-type MMTV integration site family, member 4.
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