We report a case of an SRY positive XX male. The phenotype was completely masculinised except for the reduced facial hair;testes were small, and azoospermia was present. The patient’s metaphases, coloured with acridi...We report a case of an SRY positive XX male. The phenotype was completely masculinised except for the reduced facial hair;testes were small, and azoospermia was present. The patient’s metaphases, coloured with acridine-orange to reveal the late replicating X chromosome, were sequentially hybridised with SRY and X centromeric probes: a random X chromosome inactivation pattern (XCIP) was present, with SRY present about half the time on both the active X and the inactive X. The most likely hypothesis is that the translocated SRY gene escaped inactivation as part of the entire X Pseudo Autosomal telomeric Region 1 (PAR 1). This hypothesis can explain the masculine phenotype, which would be incompatible with a halved expression of SRY. Review of the literature about the association of 46, XX males with a specific XCI pattern is made. The analysis of region AZF and QF-PCR for Y polymorphic loci allowed us to define the boundaries of the translocated Y segment as restricted to the region around the SRY locus. Chromosomal fragility analysis, using SCE (Sister Chromatid Exchanges), ruled out chromosomal fragility as a predisposing factor in the proband’s father;in addition, no chromosome Y polymorphic variant (inversion, Y qh +/﹣), was present in the proband’s father. However, like the AZF region c microdeletions and PRKX/PRKY translocation XX males, a particular Y haplotype could be also in this case a predisposing factor.展开更多
The pathogenesis of autoimmune diseases(AIDs) is characterized by a female preponderance. The causes for this sex imbalance are based on several hypotheses. One of the most intriguing hypotheses is related to an X chr...The pathogenesis of autoimmune diseases(AIDs) is characterized by a female preponderance. The causes for this sex imbalance are based on several hypotheses. One of the most intriguing hypotheses is related to an X chromosome inactivation(XCI) process. Females are mosaics for two cell populations, one with the maternal and one with the paternal X as the active chromosome. Skewed XCI is often defined as a pattern where 80% or more of the cells show a preferential inactivation of one X chromosome. The role of skewed XCI has been questioned in the pathogenesis of several AIDs, such as autoimmune thyroid diseases and rheumatoid arthritis.展开更多
Autistic spectrum disorders (ASD) occur more frequently in males, suggesting a major pathogenic role for genes located on the X-chromosome. The analysis of X chromosome inactivation (XCI) pattern may help to identify ...Autistic spectrum disorders (ASD) occur more frequently in males, suggesting a major pathogenic role for genes located on the X-chromosome. The analysis of X chromosome inactivation (XCI) pattern may help to identify XCI skewing in those families in which such genes are involved, even without identifying the specific genetic mutation. In order to identify such families, we determined the XCI pattern in 40 females with ASD and 58 mothers of children with ASD, as well as in 80 matched control females. The X inactivation assay was carried out on genomic DNA extracted from peripheral blood. XCI was calculated for informative heterozygous individuals as the ratio of the peak area of two alleles of the highly polymorphic CAG repeat of the androgen receptor (AR) gene (Xq11-12). Our results indicate that there is no difference in XCI pattern both in ASD females and in the mothers of ASD patients when compared with the appropriate controls. These findings suggest that the contribution of X-linked genes to the etiology of ASD is still likely but it is not supported by X-inactivation patterns on peripheral blood cells.展开更多
文摘We report a case of an SRY positive XX male. The phenotype was completely masculinised except for the reduced facial hair;testes were small, and azoospermia was present. The patient’s metaphases, coloured with acridine-orange to reveal the late replicating X chromosome, were sequentially hybridised with SRY and X centromeric probes: a random X chromosome inactivation pattern (XCIP) was present, with SRY present about half the time on both the active X and the inactive X. The most likely hypothesis is that the translocated SRY gene escaped inactivation as part of the entire X Pseudo Autosomal telomeric Region 1 (PAR 1). This hypothesis can explain the masculine phenotype, which would be incompatible with a halved expression of SRY. Review of the literature about the association of 46, XX males with a specific XCI pattern is made. The analysis of region AZF and QF-PCR for Y polymorphic loci allowed us to define the boundaries of the translocated Y segment as restricted to the region around the SRY locus. Chromosomal fragility analysis, using SCE (Sister Chromatid Exchanges), ruled out chromosomal fragility as a predisposing factor in the proband’s father;in addition, no chromosome Y polymorphic variant (inversion, Y qh +/﹣), was present in the proband’s father. However, like the AZF region c microdeletions and PRKX/PRKY translocation XX males, a particular Y haplotype could be also in this case a predisposing factor.
文摘The pathogenesis of autoimmune diseases(AIDs) is characterized by a female preponderance. The causes for this sex imbalance are based on several hypotheses. One of the most intriguing hypotheses is related to an X chromosome inactivation(XCI) process. Females are mosaics for two cell populations, one with the maternal and one with the paternal X as the active chromosome. Skewed XCI is often defined as a pattern where 80% or more of the cells show a preferential inactivation of one X chromosome. The role of skewed XCI has been questioned in the pathogenesis of several AIDs, such as autoimmune thyroid diseases and rheumatoid arthritis.
文摘Autistic spectrum disorders (ASD) occur more frequently in males, suggesting a major pathogenic role for genes located on the X-chromosome. The analysis of X chromosome inactivation (XCI) pattern may help to identify XCI skewing in those families in which such genes are involved, even without identifying the specific genetic mutation. In order to identify such families, we determined the XCI pattern in 40 females with ASD and 58 mothers of children with ASD, as well as in 80 matched control females. The X inactivation assay was carried out on genomic DNA extracted from peripheral blood. XCI was calculated for informative heterozygous individuals as the ratio of the peak area of two alleles of the highly polymorphic CAG repeat of the androgen receptor (AR) gene (Xq11-12). Our results indicate that there is no difference in XCI pattern both in ASD females and in the mothers of ASD patients when compared with the appropriate controls. These findings suggest that the contribution of X-linked genes to the etiology of ASD is still likely but it is not supported by X-inactivation patterns on peripheral blood cells.
