Functional insights into a rare X–autosome rearrangement: Xq23–12p13 translocation in primary amenorrhea and recurrent depression

Abstract Background Chromosomal translocations, particularly X–autosome rearrangements, are rare and can produce complex clinical phenotypes even in carriers who appear phenotypically normal. Case presentation We present a female patient with primary amenorrhea, hypergonadotropic hypogonadism, and recurrent major depressive episodes. Cytogenetic analysis revealed a previously unreported karyotype: 46,X,t(X;12)(Xpter→Xq24::12p13→12pter;Xqt er→Xq24::12p13→12qter). Array-CGH analysis confirmed that the translocation was balanced and no pathogenic copy number alterations were detected. As both parents’ karyotypes were normal, this rearrangement arose de novo. The Xq23 region contains genes involved in neuronal activity, synaptic transmission, and behaviour regulation, such as TRPC5, HTR2C, PAK3, AMMECR1, and nearby gene PLS3. The 12p13 region, on the other hand, harbours genes associated with calcium signalling, NMDA receptor function, and neurotrophic support, such as TNFRSF1A, CACNA1C, GRIN2B, FKBP4, and NTF3. PLS3 and AMMECR1 may influence cytoskeletal structure and neuronal migration. The proximity of these loci may lead to changes in gene expression through interaction with regulatory elements. This combination may explain the possible genetic basis for the simultaneous occur-rence of gonadal insufficiency, primary amenorrhoea, and neuropsychiatric findings. Computational analyses suggest that these genes may jointly modulate neuroplasticity, hypothalamic–pituitary–gonadal axis function, and neuroinflammatory responses. Conclusions This case highlights the importance of cytogenetic, molecular, and computer-assisted analyses in evaluating X–autosomal translocations in patients with unexplained amenorrhoea or recurrent depressive symptoms. Furthermore, candidate genes at breakpoints emerge as potential targets for future functional and clinical studies.