Sry-negative XX true hermaphroditism in a roe deer

A two-year-old roe deer was brought down in the course of a hunt in the north of Spain (Asturias). On physical examination the individual presented well-developed bared antlers, but surprisingly a female external genitalia. Several anatomical, histological and genetic analyses were performed in order to explain the observed phenotype. Necropsy evidenced ovary-like structures with follicles on the surface; histological analyses of testes evidenced positive immunolabel against testosterone in Leydig cells; genetic analyses showed that the sex of the individual was consistent with a female individual. PCR analysis failed to detect SRY sequences; no PIS deletion, which is responsible for XX sex-reversal in goats, was detected. On the basis of its presumptive normal female sexual karyotype (XX) and the presence of two functional abdominal bilateral testes and ovaries, the roe deer was finally diagnosed as possessing an XX hermaphroditism syndrome. However, as in many other cases, the specific reason for the occurrence of this case of hermaphroditism could not be determined.     

Familial true hermaphroditism: paternal and maternal transmission of true hermaphroditism (46,XX) and XX maleness in the absence of Y-chromosomal sequences

We report on 46,XX true hermaphroditism and 46,XX maleness coexisting in the same pedigree, with maternal as well as paternal transmission of the disorder. Molecular genetic analysis showed that both hermaphrodites as well as the 46,XX male were negative for Y-chromosomal sequences. Thus, this pedigree is highly informative and allows the following conclusions: first, the maternal as well as paternal transmission of the disorder allows the possibility of an autosomal dominant as well as an X-chromosomal dominant mode of inheritance; second, testicular determination in the absence of Y-specific sequences in familial 46,XX true hermaphrodites as well as in 46,XX males seems to be due to the varying expression of the same genetic defect; and third, there is incomplete penetrance of the defect.     

H-Y antigen expression in a case of XX true hermaphroditism

Summary Cells from an XX true hermaphrodite expressed a reduced amount of H-Y antigen when compared with normal XY cells and with cells from his father, who had an XY/XX chromosomal constitution. His mother had a normal karyotype and was H-Y negative. The four brothers of the patient were clinically and karyotypically normal. An X-Y interchange followed by random inactivation of the X chromosome is proposed to explain the H-Y antigen titer found in the patient.     

Investigation of the ZFY gene in XX true hermaphroditism and Swyer syndrome

Summary Four patients with 46,XX true hermaphroditism and one patient with 46,XY pure gonadal dysgenesis (Swyer syndrome) were analyzed with a Y chromosome-derived probe that detects a specific fragment on the short arm of the Y chromosome in the putative testicle-determining region and also a fragment on the short arm of the X chromosome. Normal males and females, an individual with Turner syndrome, and patients with various causes of anomalous gonadal differentiation accompanied by cytogenetically present Y chromosome were used as controls. The Y-specific fragment was not detected in any of the persons with 46,XX true hermaphroditism. However, this fragment was positive in the 46,XY female and in all Y-bearing patients. Cytogenetic and molecular absence of the ZFY sequence in 46,XX true hermaphrodites calls for explanations other than the classic embryogenie theory. The absence of testicular differentiation in the ZFY-positive XY female evidences functionally altered sex determination or, alternatively, defective gonadal receptors.     

A rare presentation of true hermaphroditism: an abnormal inguinoscrotal mass

This study examined the differential diagnosis of inguinoscrotal masses and true hermaphroditism as well as incarcerated inguinal hernia in the differential diagnosis of abnormal inguinoscrotal masses. Inguinoscrotal masses are a rare presentation of true hermaphroditism. A child with an inguinoscrotal mass of the right groin and penoscrotal hypospadias was diagnosed. Our case suggested that abnormal inguinoscrotal masses occur in true hermaphroditism as well as incarcerated inguinal hernia. These congenital anomalies should be considered in the differential diagnosis of inguinoscrotal masses of the groin.     

Molecular analysis in true hermaphroditism: demonstration of low-level hidden mosaicism for Y-derived sequences in 46,XX cases

True hermaphroditism (TH) is an unusual form of sex reversal, characterized by the development of testicular and ovarian tissue in the same subject. Approximately 60% of the patients have a 46,XX karyotype, 33% are mosaics with a second cell line containing a Y chromosome, while the remaining 7% are 46,XY. Molecular analyses have demonstrated that SRY is present in only 10% of TH with a 46,XX karyotype; therefore, in the remaining 90%, mutations at unknown X-linked or autosomal sex determining loci have been proposed as factors responsible for testicular development. True hermaphroditism presents considerable genetic heterogeneity with several molecular anomalies leading to the dual gonadal development as SRY point mutations or SRY hidden gonadal mosaicism. In order to identify genetic defects associated with subjects with the disease, we performed molecular analyses of the SRY gene in DNA from blood leukocytes and gonadal tissue in 12 true hermaphrodites with different karyotypes. Our results using PCR and FISH analyses reveal the presence of hidden mosaicism for SRY or other Y sequences in some patients with XX true hermaphroditism and confirms that mosaicism for SRY limited to the gonads is an alternative mechanism for testicular development in 46,XX true hermaphrodites.     

Alpha-globin gene cluster haplotypes in the Kalahari San and southern African Bantu-speaking blacks.

Alpha-globin gene cluster haplotypes were determined in Southern African San and negroid populations. Significant differences (P less than .01) between the two groups were found at three of the nine loci in the cluster. The most striking difference, however, was the relatively low level of variation found in the San (alpha alpha)-associated haplotypes and the high level in the SA blacks. This trend was also observed for the 3' hyper-variable region. Nineteen different haplotypes were identified among the 36 haplotypes studied in the black population, but only seven different ones were found among the 37 haplotypes in the San; five were common to both populations. The common San haplotype, (+--MPZ+---), had a frequency of .57 in the San and .11 in the black population; the common SA black haplotype, (---MZ----), occurred at a frequency of .17 but was absent in the San. In the SA black population significant linkage disequilibrium is present between five of the RFLP loci, including the extreme 5' and 3' markers, confirming the absence of a recombination hot spot in the alpha-globin gene cluster.     

A case of true hermaphroditism reveals an unusual mechanism of twinning

Traditionally twins are classified as dizygous or fraternal and monozygous or identical (Hall Twinning, 362, 2003 and 735-743). We report a rare case of 46,XX/46,XY twins: Twin A presented with ambiguous genitalia and Twin B was a phenotypically normal male. These twins demonstrate a third, previously unreported mechanism for twinning. The twins underwent initial investigation with 17-hydroxyprogesterone and testosterone levels, pelvic ultrasound and diagnostic laparoscopy. Cytogenetic analysis was performed on peripheral blood cells and skin fibroblasts. Histological examination and Fluorescence in situ hybridization studies on touch imprints were performed on gonadal biopsies. DNA analysis using more than 6,000 DNA markers was performed on skin fibroblast samples from the twins and on peripheral blood samples from both parents. Twin A was determined to be a true hermaphrodite and Twin B an apparently normal male. Both twins had a 46,XX/46,XY chromosome complement in peripheral lymphocytes, skin fibroblasts, and gonadal biopsies. The proportion of XX to XY cells varied between the twins and the tissues evaluated. Most significantly the twins shared 100% of maternal alleles and approximately 50% of paternal alleles in DNA analysis of skin fibroblasts. The twins are chimeric and share a single genetic contribution from their mother but have two genetic contributions from their father thus supporting the existence of a third, previously unreported type of twinning.     

The role of the sex-determining region of the Y chromosome (SRY) in the etiology of 46,XX true hermaphroditism

Summary The syndrome of 46,XX true hermaphroditism is a clinical condition in which both ovarian and testicular tissue are found in one individual. Both Mullerian and Wolffian structures are usually present, and external genitalia are often ambiguous. Two alternative mechanisms have been proposed to explain the development of testicular tissue in these subjects: (1) translocation of chromosomal material encoding the testicular determination factor (TDF) from the Y to the X chromosome or to an autosome, or (2) an autosomal dominant mutation that permits testicular determination in the absence of TDF. We have investigated five subjects with 46,XX true hermaphroditism. Four individuals had a normal 46,XX karyotype; one subject (307) had an apparent terminal deletion of the short arm of one X chromosome. Genomic DNA was isolated from these individuals and subjected to Southern blot analysis. Only subject 307 had Y chromosomal sequences that included the pseudoautosomal boundary, SRY (sex-determining region of Y), ZFY (Y gene encoding a zinc finger protein), and DXYS5 (an anonymous locus on the distal short arm of Y) but lacked sequences for DYZ5 (proximal short arm of Y) and for the long arm probes DYZ1 and DYZ2. The genomic DNA of the other four subjects lacked detectable Y chromosomal sequences when assayed either by Southern blotting or after polymerase chain reaction amplification. Our data demonstrate that 46,XX true hermaphroditism is a genetically heterogeneous condition, some subjects having TDF sequences but most not. The 46,XX subjects without SRY may have a mutation of an autosomal gene that permits testicular determination in the absence of TDF.     

Report of a case of true hermaphroditism with karyotype 45,X/46,XX/46,X,mar/47,XX,mar

The case of a 24-year-old man with hypoplastic external genitalia, lack of the right scrotal testis and gynaecomastia has been described. In the intermitotic cells the cytogenetic investigations revealed the presence of the X body and the absence of the Y body. A 45,X/46,XX/46,X,mar/47,XX,mar karyotype could be established. On laparotomy a rudimentary ovary, uterus and vagina were detected on the right side of the abdominal cavity.     

Morphologic and hormonal correlates of true hermaphroditism in the rabbit

A macro-microscopical and histological investigation of the urogenital system organs of a rabbit-hermophrodite has been performed with an aim to compare the content of sex steroids in the peripheral and in the gonadal blood estimated by means of radioimmunological methods. Certain anomalies have been found out in the development of external and internal sex organs, kidneys and urinary bladder. Testosterone and estradiol concentration in blood flowing from the ovotestis is decreased, as it is in the periphral blood. The rabbit urogenital system organs have been studied from the 12th day of the intrauterine development up to the 10th day of the postnatal life. The results of the investigation performed make it possible to consider that the developmental anomalies in the rabbit-hermophrodite have, evidently, appeared between the 20th--25th days of its intrauterine development as a result of certain disbalance of sex steroids.     

SRY-negative true hermaphrodites and an XX male in two generations of the same family

Two 46,XX true hermaphrodites and one XX male without genital ambiguities are reported. They coexist in two generations of the same pedigree, with paternal transmission and in the absence of SRY (sex-determining region, Y chromosome). These familial cases provide evidence to support the hypothesis that these disorders are alternative manifestations of the same genetic defect, probably an autosomal dominant mutation (with incomplete penetrance) or an X-linked mutation (limited by the presence of the Y chromosome).     

Population genetics of alpha-1-antitrypsin polymorphism in US whites, US blacks and African blacks.

An isoelectric focusing (IEF) procedure in an ultra-narrow pH range, 4.2-4.9, has been utilized to detect alpha 1-antitrypsin or alpha 1-protease inhibitor (PI) allele products in 2 US white and 3 US black populations as well as 1 native African black population. In addition to the 3 common alleles PI*M1, PI*M2 and PI*M3, products of the 4th allele PI*M4 have been identified in US whites at low-level frequency. The presence of the PI*S, PI*Z and PI*I alleles has also been verified in our population samples. While the PI*S allele is present at a polymorphic level in US whites, it is only present sporadically in US blacks and is completely absent in African blacks. The PI*Z allele was not detected in the black populations tested. The PI allele frequency data have been used to calculate white admixture in US blacks.     

tRNA nucleotide 47: an evolutionary enigma.

A previous analysis of tRNA sequences suggested a correlation between the absence of a nucleotide at position 47 (nt 47) in the extra loop and the presence of a U13:G22 base pair in the D-stem. We have evaluated the significance of this correlation by determining the in vivo activity of tRNAs containing either a C13:G22 or a U13:G22 pair in tRNA molecules with or without nt 47. Although this correlation might reflect some malfunction of tRNAs lacking nt 47, but containing the C13:G22, assays of the in vivo suppressor activity showed that this tRNA is actually more active than the tRNA with the features found in the database, i.e., a U13:G22 base pair and no nt 47. Moreover, analogous constructs with a GGC anticodon permitted the growth of an Escherichia coli strain deleted for tRNA(Ala)GGC genes equally well. On the other hand, long-term growth experiments with competing E. coli strains harboring the tRNA lacking nt 47, either with the C13:G22 or the U13:G22 base pair demonstrated that the U13:G22 tRNA overtook the C13:G22 strain even when the starting proportion of strains favored the C13:G22 strain. Thus, the preference for the U13:G22 tRNA lacking nt 47 in the sequence database is most likely due to factors that come into play during extended growth or latency rather than to the ability of the tRNA to engage in protein synthesis.     

Fish species diversity in southern African estuarine systems: an evolutionary perspective

Synopsis The ichthyofauna of southern African estuaries consists primarily of juvenile marine species that use these habitats as nursery areas. The abundance and biomass of fishes in estuarine systems are typically high but species diversity is generally low, with only a few taxa dominating the community. This relatively low species diversity is attributed to the fact that estuaries in the region are unpredictable environments which lack any degree of permanence and are dominated by mobile marine eurytopes. Although stenotopes, represented mainly by small resident species from the families Gobiidae, Clinidae and Syngnathidae, are present in southern African estuaries, little speciation appears to have occurred. A possible reason for this lack of speciation, apart from the seasonal and annual variability of the abiotic environment, is that the lifetime of individual systems is usually limited to a few thousand years. In addition, fishes utilising southern African estuaries need to remain flexible (eurytopic) in their responses to an external environment which is unlikely to become more stable in the future. Thus the lack of permanence and fluctuating nature of southern African estuaries on both a spatial and temporal scale, together with the dominance of eurytopes in these systems, does not favour the evolution of new species. A preliminary examination of the available literature indicates that a detailed review of estuarine ichthyofaunal communities on a global basis will probably mirror the trends outlined above, and reveal a domination of these dynamic ecosystems by eurytopic taxa with low speciation potential.     

Evolutionary origin of SL-addition trans-splicing: still an enigma.

Spliced-leader (SL) trans-splicing is an essential step in pre-mRNA maturation in a variety of lower eukaryotic organisms. However, this processing pathway is absent in mammals, insects, yeast and plants. The patchy phylogenetic distribution of SL trans-splicing is consistent with either ‘multiple gain’ or ‘multiple loss’ evolutionary scenarios. Recent studies show that two additional metazoan phyla carry out SL trans-splicing, significantly increasing its phylogenetic range. However, it remains unclear whether this unusual type of splicing is an ancestral or an acquired trait.     

Calcaneal measurement in estimation of stature of South African blacks

Stature (height) is an important factor in establishing the identity of a person in the living as well as in the skeletonized state. When stature is estimated from the bones of the limbs, regression equations, which estimate the ratios of the lengths of bones to the height of the individual, are generated. The majority of bones that were used previously were the long bones. The calcaneus was used for estimating stature only in American whites and blacks (Holland [1995] Am. J. Phys. Anthropol. 96:315-320). The regression equations that he generated were found to be useful for stature estimation in these population groups. Since the calcaneus has not been used for the same purpose in South Africa, the aim of this study was to derive regression equations that will allow this bone to be used for stature estimation in South African blacks. In total, 116 complete skeletons (60 males and 56 females) were selected from the Raymond A. Dart Collection of Human Skeletons, School of Anatomical Sciences, University of the Witwatersrand (Johannesburg, South Africa). The skeletal heights of these sets of skeletons were calculated using the anatomical method of Fully ([1956] Ann. Med. Leg. 35:266-273). Nine parameters of the calcaneus were measured and matched against skeletal heights, using univariate and multivariate regression methods. Regression equations were obtained for estimation of the stature of the South African black population from the calcaneus. The standard error of estimate that was obtained with univariate regression analysis was higher than the corresponding values using multivariate regression analysis. In both cases, the standard errors of estimate compared well with the values obtained for fragmentary long bones by previous authors.     

Same sexual system but variable sociobiology: evolution of protandric simultaneous hermaphroditism in Lysmata shrimps

The sexual system of the decapod (caridean) shrimp Lysmata isprotandric simultaneous hermaphroditism (PSH). Individuals firstmature as males (male phase = MP) and then when older (larger)change to the external phenotype of female carideans (femalephase = FP). However, unlike purely protandric carideans, LysmataFPs retain reduced male gonadal tissues and ducts, and are ableto mate nonreciprocally as males as well as to reproduce asfemales. Thus, FPs of Lysmata species are functional simultaneoushermaphrodites although most reproductive effort is devotedto embryo production and incubation. The question explored hereis, given the propensity of carideans to protandry, the apparentlow cost, and high reproductive advantage of PSH, why has notPSH evolved more frequently? The mating systems and sexual selectionof caridean shrimps, the original sex of protandric individuals,the cost of maleness, and sex allocation theory are discussedin relation to protandry and PSH. None of these factors adequatelyexplains the evolution of PSH of Lysmata species. Lysmata hasat least 2 species groups with very different sociobiologies;these groups do not appear to share current selective pressuresthat would explain PSH in both. A historical contingency hypothesis,testable in part with a phylogenetic analysis, may explain theevolution of PSH in Lysmata.