SRVX, a sex reversing locus in Xp21.2?p22.11

Abstract

Duplication within Xp21 causes female or intersexual development in human embryos with an XY chromosome complement. We have mapped the responsible gene, SRVX (sex reversal X), in XY-sex-reversed maternal half siblings who had inherited the duplication from their mother. The limited size of the duplication in our cases, relative to its extent in other similar cases, allows assignment of the SRVX locus to Xp21.2-->p22.11. We infer that SRVX is part of a pathway of sex-determining genes that includes SRY and SRA1, the latter recently assigned to chromosome 17q. If mutation of SRA1 or SRVX can reverse the sex of the XY fetus, this would explain why mutation within SRY is found only sporadically in women with XY gonadal dysgenesis.

ApoO, a Novel Apolipoprotein, Is an Original Glycoprotein Up-regulated by Diabetes in Human Heart

“…Chromosomal localization of apoO was found at Xp22.11 in Entrez Gene (NCBI). This chromosomal location is a locus related to X-linked mental retardation (43) and the sex-reversing locus (44). The apoO gene was precisely localized by sequencing at this locus between the spermidine/spermine N 1 -acetyltransferase and the eukaryotic translation initiation factor 2 (45).…”

Genes envolvidos na determinação e diferenciação do sexo

“…Em indivíduos 46,XY a duplicação de uma região no braço curto do cromossomo X chamada DSS (Dosage Sensitive Sex reversal, localizado em Xp21) causa disgenesia gonadal e sexo reverso independentemente da presença do SRY, enquanto que a deleção desse locus não afeta a diferenciação testicular (72)(73)(74)(75)(76). Por outro lado, a duplicação da região DSS em um dos cromossomos X de mulheres 46,XX não afeta a diferenciação ovariana.…”

X-linked sex-reversing genes

“…The gene was located in the segment Xp22.11 → p21.2, comprising some 10 megabases of DNA distal to the OTC locus and including ZFX and DMD (see also Ogata and Matsuo, 1994). We inferred (i) that perturbation of the new gene, as in cases of Xp duplication, could block differentiation of the testis despite presence of an intact SRY sequence; (ii) that some cases of XY gonadal dysgenesis could be due to submicroscopic duplications within SRVX; and (iii) that SRVX was part of a pathway of testisdetermining genes that included SRY (Arn et al, 1994). Markers are shown in the flanking lanes.…”

“…XY sex reversal was due to a duplication in Xp22.11 → p21.2, inherited from the mother. Case report in Arn et al (1994).…”

“…A "primary" sex-reversing gene on Xp Arn et al (1994) described a small duplication within Xp in a mother and her two sex-reversed XY children, each sired by a different father (Fig. 2).…”