Chimerism as the etiology of a 46,XX/46,XY fertile true hermaphrodite

Verp, Marion S.; Harrison, Harold H.; Ober, Carole; Oliveri, Douglas R.; Amarose, Anthony P.; Lindgren, Valerie; Talerman, Aleksander

doi:10.1016/s0015-0282(16)54843-2

Cited by 50 publications

(19 citation statements)

References 14 publications

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“…OT-DSD is usually present at birth with ambiguous genitalia, and the majority of patients show a 46,XX karyotype with absence of the SRY sequence [Ramsay et al, 2009]. The origin of this condition may be due to undetected 46,XX/46,XY chimerism as a result of fertilization of the ovum and the polar body or tetragametic fusion [Verp et al, 1992;Berger-Zaslav et al, 2009], or it may also result from mutations of autosomal or X chromosome genes involved in the testis-determining pathway [Raine et al, 1989;SalasCortés et al, 2000;Sekido and Lovell-Badge, 2008]. ( fig.…”

Section: Discussionmentioning

confidence: 99%

Sex Chromosome Mosaicism in the Gonads of DSD Patients: A Karyotype/Phenotype Correlation

Kamel

El-Ghany²,

Mekkawy³

et al. 2015

Sex Dev

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Sex chromosome mosaicism results in a large clinical spectrum of disorders of sexual development (DSD). The percentage of 45,X cells in the developing gonad plays a major role in sex determination. However, few reports on the gonadal mosaic status have been published, and the phenotype is usually correlated with peripheral lymphocyte karyotypes, which makes the phenotype prediction imprecise. This study was conducted on 7 Egyptian DSD patients to demonstrate the effect of sex chromosome constitution of both blood lymphocytes and gonadal tissues on the phenotypic manifestations. Conventional cytogenetic and FISH analyses of blood lymphocytes were conducted, and laparoscopy with gonadal biopsy was performed for histopathologic examination and FISH analysis. Gonosomal mosaicism was detected in 3 patients who had a non-mosaic chromosome pattern in blood lymphocytes. Two patients showed the same type of sex chromosome mosaicism in both the blood and gonadal tissues but with different distributions. Two other patients revealed a non-mosaic pattern in both tissues. The present study elucidates the importance of examining sex chromosome mosaicism in gonadal tissues of DSD patients and highlights the critical role of 45,X mosaicism which can lead to serious effects during early gonadal organogenesis.

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Section: Discussionmentioning

confidence: 99%

Sex Chromosome Mosaicism in the Gonads of DSD Patients: A Karyotype/Phenotype Correlation

Kamel

El-Ghany²,

Mekkawy³

et al. 2015

Sex Dev

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“…Examples of chimerism and tetragametism, have been found in mice [58][59][60], and other mammals [61] including humans [62][63][64][65][66]. Affected persons are identified by the production of two populations of cells in all tissues, or/and ambiguous genitalia and hermaphroditism alone or in combination [67].…”

Section: Fusion Of Embryosmentioning

confidence: 99%

Chimerism and tetragametic chimerism in humans: implications in autoimmunity, allorecognition and tolerance

et al. 2007

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The presence of cells or tissues from two individuals, chimeras, or the presence of cells and tissues that include the gonads, tetragametic chimerism can be detected by the analysis of cytogenetics and analysis of polymorphic genetic markers, using patterns of pedigree inheritance. These methodologies include determination of sex chromosomes, major histocompatibility complex (MHC) polymorphisms and panels of short tandem repeats (STRs) that include mitochondrial DNA markers. Studies routinely involve cases of temporal chimerism in blood transfusion, or following allotransplantation to measure the outcome of the organ, lymphopoietic tissues or bone marrow grafts. Demonstration of persistent chimerism is usually discovered in cases of inter-sexuality due to fusion of fraternal twins or in cases of fusion of embryos with demonstrable allogeneic monoclonality of blood which, excluded maternity or paternity when blood alone is used as the source of DNA. In single pregnancies it is possible to produce two kinds of microchimerism: feto-maternal and materno-fetal, but in cases of fraternal twin pregnancies it is possible to identify three different kinds which are related to cases of vanishing twins that can be identified during pregnancy by imaging procedures; (1) hematopoietic, (2) gonadal, and (3) freemartins when the twins have different sex and the individual born is a female with either gonadal or both gonadal and hematopoietic tissues. Fraternal twin pregnancies can also produce fusion of embryos. Such cases could be of different sex presenting with inter-sexuality or in same sex twins. One of such cases, the best studied, showed evidence of chimerism and tetragametism. In this regard, the case was studied because of disputed maternity of two of her three children. All tissues studied, except for the blood, demonstrated four genetic components but only two in her blood of four possible showed allogeneic monoclonality consistent with the interpretation that her blood originated from one hematopoietic stem cell. Also, microchimerism, due to traffic of cells via materno-fetal or feto-maternal has been prompted by reports of their potential association with the development of autoimmune disorders including systemic lupus erythematosus (SLE) and systemic sclerosis, and in allotransplantation. In addition, their relevance of chimerism in the positive and negative selection of T cells in the thymus has not been addressed. T lymphocytes play a central role in controlling the acquired immune response and furthermore serve as crucial effector cells through antigen specific cytotoxic activity and the production of soluble mediators. Central tolerance is established by the repertoire selection of immature T lymphocytes in the thymus, avoiding the generation of autoreactive T cells. Expression of chimeric antigens in the thymus could modify the generation of specific T cell clones in chimeric subjects and these mechanisms could be important in the induction of central tolerance against foreign antigens important in allo-transp...

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“…As the gonads are dysgenetic and nonfunctional, spontaneous pubertal development seldom occurs in these women (12), and successful pregnancy is even more unusual; unassisted pregnancy is unheard of (1). There have been a few instances of fertility in 46,XX/46,XY true hermaphrodites (13), but no reports of fertility in a 46,XY woman.…”

Section: Introductionmentioning

confidence: 99%

“…Pregnancy in Turner Syndrome is reported to be possible in about 2% of cases (13), though it is rare for unassisted pregnancy to occur in non- …”

Section: Introductionmentioning

confidence: 99%

Report of Fertility in a Woman with a Predominantly 46,XY Karyotype in a Family with Multiple Disorders of Sexual Development

Dumić

New²,

Lin‐Su³

et al. 2011

Advances in Experimental Medicine and Biology

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Context: We report herein a remarkable family in which the mother of a woman with 46,XY complete gonadal dysgenesis was found to have a 46,XY karyotype in peripheral lymphocytes, mosaicism in cultured skin fibroblasts (80% 46,XY and 20% 45,X) and a predominantly 46,XY karyotype in the ovary (93% 46,XY and 6% 45,X).Patients: A 46, XY mother who developed as a normal woman, underwent spontaneous puberty, reached menarche, menstruated regularly, experienced two unassisted pregnancies, and gave birth to a 46,XY daughter with complete gonadal dysgenesis.

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Chimerism as the etiology of a 46,XX/46,XY fertile true hermaphrodite

Cited by 50 publications

References 14 publications

Sex Chromosome Mosaicism in the Gonads of DSD Patients: A Karyotype/Phenotype Correlation

Sex Chromosome Mosaicism in the Gonads of DSD Patients: A Karyotype/Phenotype Correlation

Chimerism and tetragametic chimerism in humans: implications in autoimmunity, allorecognition and tolerance

Report of Fertility in a Woman with a Predominantly 46,XY Karyotype in a Family with Multiple Disorders of Sexual Development

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