Chimerism in Black Southern African Patients with True Hermaphroditism 46,XX/47XY,+21 and 46,XX/46,XY

Abstract

True hermaphroditism is defined by the presence of both testicular and ovarian tissue in an individual. True hermaphrodites usually present at birth with ambiguous genitalia, and subsequent invasive investigations are needed to confirm the diagnosis. Several large cohorts of black South Africans with true hermaphroditism have been described, and by far the majority of those investigated had a 46,XX karyotype, with absence of the SRY sequence. This paper represents the first report of the molecular investigation of mosiacism/chimerism as the cause of hermaphroditism in black southern African patients. It is the second report worldwide of a 46,XX/47,XY,+21 chimera, with the first described in a Japanese infant in 1994. Case 1 in the present study is a child who is a 46,XX/47,XY,+21 tetragametic chimera. Molecular studies revealed two paternal and two maternal alleles at four of ten STR loci investigated and three alleles at four of these loci. The young boy exhibited no features of Down syndrome, other than a unilateral single palmar crease. Cases 2 and 3 both have a 46,XX/46,XY karyotype. Chimerism is supported by molecular analysis in Case 2, and molecular studies were not done for Case 3.

Meiotic errors followed by two parallel postzygotic trisomy rescue events are a frequent cause of constitutional segmental mosaicism

“…in case of a mosaic all autosomal genotypes outside the duplicated region are expected to only contain two alleles (1 maternal & 1 paternal). For chimeras, some loci would have three or four alleles, or a skewed dosage of two alleles [37]. None of the samples showed more than two alleles on any of the markers, confirming the mosaic status of the aberration (data not shown).…”

Multiparameter Investigation of a 46,XX/46,XY Tetragametic Chimeric Phenotypical Male Patient with Bilateral Scrotal Ovotestes and Ovulatory Activity

“…The subsequent observed formation of gonadal cysts leading to enlargement of the remaining scrotal gonad after complete unilateral gonadectomy has also been previously reported in a 13 years-old patient, also showing (recurrent) gynecomastia [Cook and Gashti, 1979]. Moreover, the presence of lighter and darker skin pigmented patches in a male with ambiguous genitalia following the Blaschko's lines, a XX/XY chromosomal pattern, and OT-DSD has been reported before as well [Ramsay et al, 2009]. These observations match the specific combination of characteristics identified in the patient described here, i.e., gynecomastia, (recurrent) gonadal cysts, and the Blaschko's lines.…”

The identification of a spontaneous 47, XX, +21/46, XY chimeric fetus with male genitalia

“…Recently, in vitro fertilization appears to increase the incidence of tetragametic chimeras [8,9] because standard practices necessitate the utilization of more than one embryo to increase success rates. Molecular analyses have been performed for 2 [4,7] of the 4 previously reported cases with sex chromosome discordant chimerism with trisomy 21. Both were tetragametic chimeras and revealed a paternal origin of the extra 21 st chromosome.…”

“…One was a true hermaphrodite [4], one was a newborn infant with ambiguous genitalia [5], and other two cases had normal gonads [6,7]. Three cases harbored an extra chromosome 21 in their XY lineages [4-6], and one case had mosaicism in the XX lineage [7]. Here, we present the fifth case of sex-chromosome discord4nt chimerism, with trisomy 21 (47, XX + 21/46, XY) and male genitalia.…”