A case of ring Y chromosome

Summary Ring Y chromosome 45,X/46,X,r(Y) was identified by fluorescence in a child with ambiguous external genitalia, urogenital sinus, vagina, uterus, and Fallopian tubes. Testicular tissue was noted on gonadal biopsy.     

Sexual ambiguity and a non-fluorescent Y chromosome

The personal experience in three patients with ambiguous external genitalia and 45,X/46,XYnf karyotype is reported. The different clinical and cytogenetic aspects of this entity are described and discussed.     

A case of true hermaphroditism with 45X/46XY mosaicism

Summary The authors describe a case of true hermaphroditism of mainly female phenotype, ambiguous external genitalia, and ovotestis. The cytogenetic studies revealed 45X/46XY mosaicism and an absence of Barr bodies.     

Arhopalus ferus (Coleoptera: Cerambycidae): structure and function of the female reproductive system

Abstract

Arhopalus ferus (Mulsant) female pupae and adults were dissected, and both internal and external genitalia are described. The external genitalia involve segments 8 and 9. Segment 9 and its appendages are modified into a long ovipositor which telescopes with segment 8 into segment 7 when retracted. The internal genitalia include ovaries, bursa copulatrix, spermatheca, spermathecal gland, vagina, and accessory glands. The terminology applied to coleopteran genital anatomy is critically discussed.     

A case of ambiguous genitalia presenting with a 45,X/46,Xr(Y)(p11.2;q11.23)/47,X,idic(Y)(p11.2),idic(Y)(p11.2) karyotype

An infant with ambiguous genitalia was found to have a karyotype 45,X/46,X,r(Y)(p11.2;q11.23)/47,X,idic(Y)(p11.2),idic(Y)(p11.2) using G-banding, C-banding and FISH. Examination of the genitalia revealed a phallus measuring 1.5 cm in length and 0.5 cm wide with perineal orifice. Subtle phenotypic features consistent with Turner syndrome were not present. Genital ultrasonography revealed the presence of an infantile uterus. Endoscopy of the vagina, uterus and cervix appeared normal.     

True hermaphroditism in a phenotypic male without ambiguous genitalia: an unusual presentation at puberty

True hermaphroditism usually appears with ambiguous genitalia requiring extensive evaluation during the neonatal period. There have been occasional cases with better differentiation of external genitalia, leading to delays in diagnosis. We report the case of an adolescent boy with true hermaphroditism who presented with normal external genitalia and no sexual ambiguity. He was referred due to progressive gynecomastia and arrest of puberty. He presented at the age of 16 years for gynecomastia of rapid progression with normal penile development and both gonads in scrotum and normal testosterone and increased gonadotropin levels. Gonadal ultrasound scan was compatible with testicular and ovarian tissues in scrotum, and the karyotype showed two cellular lines (46,XX/46,XY). Gonadal histology revealed bilateral ovotestes. A genotype polymerase chain reaction mediated analysis using seven microsatellite markers did not confirm chimerism. Clinical findings and mechanism of generation are discussed.     

SRY-negative XX sex reversal in a pony: a case report

A three year old pony with sexually ambiguous external genitalia was found to have a normal female karyotype (64, XX) and bilateral inguinal testes. The PCR analysis of blood samples revealed the absence of the Y chromosome sequences SRY, eTSPY and ZFY. No Y chromosome sequences were identified in DNA extracted from the gonads. The mechanism whereby XX sex reversal occurs in the absence of SRY is unknown.     

Cryptic Genomic Rearrangements in Three Patients with 46,XY Disorders of Sex Development

Background

46,XY disorders of sex development (46,XY DSD) are genetically heterogeneous conditions. Recently, a few submicroscopic genomic rearrangements have been reported as novel genetic causes of 46,XY DSD.

Methodology/Principal Findings

To clarify the role of cryptic rearrangements in the development of 46,XY DSD, we performed array-based comparative genomic hybridization analysis for 24 genetic males with genital abnormalities. Heterozygous submicroscopic deletions were identified in three cases (cases 1–3). A ∼8.5 Mb terminal deletion at 9p24.1–24.3 was detected in case 1 that presented with complete female-type external genitalia and mental retardation; a ∼2.0 Mb interstitial deletion at 20p13 was identified in case 2 with ambiguous external genitalia and short stature; and a ∼18.0 Mb interstitial deletion at 2q31.1–32 was found in case 3 with ambiguous external genitalia, mental retardation and multiple anomalies. The genital abnormalities of case 1 could be ascribed to gonadal dysgenesis caused by haploinsufficiency of DMRT1, while those of case 3 were possibly associated with perturbed organogenesis due to a deletion of the HOXD cluster. The deletion in case 2 affected 36 genes, none of which have been previously implicated in sex development.

Conclusions/Significance

The results indicate that cryptic genomic rearrangements constitute an important part of the molecular bases of 46,XY DSD and that submicroscopic deletions can lead to various types of 46,XY DSD that occur as components of contiguous gene deletion syndromes. Most importantly, our data provide a novel candidate locus for 46,XY DSD at 20p13.     

Combined cytogenetic techniques and non-fluorescent Y. Cytologic evidences of dic(Yp)(q11) in a previously interpreted 46,X,Yq-

mos 45,X/46,X,Y with no bright fluorescence was studied in 4 patients presenting variable phenotypes, from Turner's syndrome, with or without virilization, to ambiguous external genitalia, with combined cytogenetic techniques. G-11 staining demonstrated, in all cases, that the abnormal Y was a dic(Yp). Considerations about the possibility that some of the 46,X,Yq-males attending infertility clinics may be examples of dic(Yp) are made.     

A male infant with monosomy 21.

A male infant with total monosomy 21 identified by Q-, G- and R-banding is described. His main symptoms are hypertonia, micrognathia, microphthalmus, imperforate anus, ambiguous external genitalia, floating and malopposed thumbs, overlying fingers, right clubfoot and growth retardation. Both parents are phenotypically as well as karotypically normal.     

True hermaphroditism in a child with a chimeric XX/XY chromosome, a double erythrocyte population and an unusual Lewis (a+ b+) phenotype

A 2 years-old Korean girl is seen because of ambiguous external genitalia. Surgical exploration shows the right gonad to be an ovary and the left one to be an ovotestis, thus demonstrating a true hermaphroditism. Cytogenetic studies of peripheral lymphocytes reveal a mixture of 46,XX and 46,XY cells, with a predominant XX cell line. The patient's red cells are composed of two distinct populations differing in three genetically independent blood group systems. The ratios of the two cell lines in various tissues, especially among the cells secreting Lewis antigens, appear to be very different and suggest several hypothesis to explain the highly unusual red cell Lewis phenotype Le (a+ b+). We conclude to a dispermic chimera, however the adopted status of this child prevents any identification of the maternal or paternal contributions. Because of the physical aspect it was decided to remove the ovotestis, to repair the external genitalia and to bring up this child as a female.     

Xp-duplications with and without sex reversal

Duplications in Xp including the DSS (dosage sensitive sex reversal) region cause male to female sex reversal. We investigated two patients from families with Xp duplications. The first case was one of two sisters with karyotype 46,XY, der(22), t(X;22)(p11.3;p11)mat and unambiguous female genitalia. The living sister was developmentally retarded, and showed multiple dysmorphic features and an acrocallosal syndrome. The second case was a boy with a maternally inherited direct duplication of Xp21.3-pter with the breakpoint close to the DSS locus. He had multiple abnormalities and micropenis, but otherwise unambiguous male genitalia. We performed quantitative Southern blot analysis with probes from Xp22.13 to p21.2 to define the duplicated region. Clinical, cytogenetic, and molecular data from both patients were compared with those of previously reported related cases. A comparison of the extragenital symptoms revealed no differences between patients with or without sex reversal. In both cases, the symptoms were non-specific. Among 22 patients with a duplication in Xp, nine had unambiguous female genitalia and a well-documented duplication of the DSS region. Two patients with duplication of DSS showed ambiguous external genitalia. From these data, we conclude that induction of testicular tissue may start in these patients, but that the type of genitalia depends on the degree of subsequent degeneration by a gene in DSS.     

Familial XX true hermaphroditism and the H-Y antigen

Summary Two 46,XX sibs, one of female, one of male gender, and both with ambiguous external genitalia and ovotestis, were H-Y positive. The mother was H-Y negative. It is assumed that the underlying mutation was transmitted by the father, resulting in an autosomal dominant mode of inheritance. The common origin and the nature of the mutation leading to XX sex reversal are discussed.     

Ambiguous genitalia by 9p deletion inherent to a dic(Y;9)(q12;p24)

We describe here a 3-month-old male infant with brachy-plagyocephaly, short neck, widely spaced nipples, mild hypertonia, and ambiguous external genitalia but with both testes in the scrotum and no Müllerian derivates. His karyotype was 45,X,der(Y;9)(q12;p24).ish der(Y;9)(DYZ3+,SRY+,9ptel-) de novo. This patient's impaired sex differentiation is consistent with gonadal dysgenesis and compares with the male-to-female sex reversal secondary to a partial 9p deletion in spite of an intact Yp or SRY locus documented in 24 patients including a sex-reversed girl with a (Y;9) dicentric derivative. As for the cytogenetic findings, this case represents the second instance of a de novo pseudodicentric (Y;9) chromosome with loss of both distal 9p and Yq12 regions, apparent intactness of SRY, and consistent or preferential inactivation of the Y centromere. In addition, the possible 9p23p-p22 duplication observed in this case evokes the concomitant 9p22-p21 duplication documented in the previous girl with a (Y;9) derivative. Hence, these striking similarities point to a nonrandom Y;9 rearrangement in patients with either sex reversal or gonadal dysgenesis. Even if the present pseudodicentric derivative had inactivated the Y centromere, the existence of some variant cells points to functional dicentricity as it has been documented in other Y;autosome dicentric derivatives.     

Sex reversal due to Xp disomy by t(X;Y)(p21;q11).

A 20-month-old infant exhibiting psychomotor retardation, dysmorphisms and ambiguous external genitalia was found to have a 46-chromosome karyotype including a normal X chromosome and a marker Y with most of Yq being replaced by an extra Xp21-->pter segment. The paternal karyotype (G and C bands) was 46,XY. The marker Y composition was verified by means of FISH with a chromosome X painting, an alphoid repeat and a DMD probe. Thus, the final diagnosis was 46,X,der(Y)t(X;Y)(p21;q11)de novo.ish der(Y)(wcpX+,DYZ3+,DMD+). The patient's phenotype is consistent with the spectrum documented in 13 patients with similar Xp duplications in whom sex reversal with female or ambiguous genitalia has occurred in spite of an intact Yp or SRY gene. A review of t(X;Y) identifies five distinct exchanges described two or more times: t(X;Y)(p21;q11), t(X;Y)(p22;p11), t(X;Y)(p22;q11-12), t(X;Y) (q22;q12), and t(X;Y)(q28;q12). These translocations probably result from a recombination secondary to DNA homologies within misaligned sex chromosomes in the paternal germline with the derivatives segregating at anaphase I.     

Abnormal gonadal differentiation in two subjects with ambiguous genitalia,Mullerian structures,and normally developed testes: Evidence for a defect in gonadal ridge development

Among a group of patients with abnormal sexual differentiation, we have identified two subjects who had a 46,XY karyotype, ambiguous genitalia, and well-developed Müllerian structures, but normal appearing testes. The presence of ambiguous genitalia and persistent Müllerian structures implied both Leydig cell and Sertoli cell dysfunction, hence, gonadal dysgenesis. However, the normal testicular histology suggested that the underlying abnormality was not a defect in testis determination itself but an abnormality in timing of gonadal ridge and testis development. In one of the two subjects genomic DNA was available. The sequence of the SRY gene was normal. Because rare patients with partial androgen insensitivity may have a similar phenotype, the AR gene was evaluated by denaturing gradient gel electrophoresis (DGGE) and was normal. Some subjects with mutation of the WT1 gene or with deletion of the distal short arm of chromosome 9 may have similar phenotypes. The WT1 gene was studied by single-strand conformation polymorphism (SSCP) analysis and was normal. In addition, there was no loss of heterozygosity of polymorphic markers in distal 9p. The gene for Müllerian inhibiting substance (MIS) was also studied by SSCP and was normal. Although the exact mechanism for the defect in the two subjects is unknown, it may be due to an abnormality in a gene or genes involved in the timing of gonadal ridge development. Received: 5 August 1994 / Revised: 25 January 1995, 3 April 1995     

Prenatal prediction of androgen insensitivity syndrome using exon 1 polymorphism of the androgen receptor gene.

Exon 1 polymorphism of the androgen receptor (AR) gene is characterized by a (CAG)n(CAA) repeat at position 172 following the translation start codon. The aim of this study was to determine whether AR gene exon 1 polymorphism could be used to perform prenatal diagnosis in high risk families with complete or partial androgen insensitivity syndrome. After enzymatic amplification of a 1 kilobase exon 1 fragment, each DNA was simultaneously digested by MspI and PstI restriction enzymes. After electrophoresis on a 15% electrophoresis on a 15% acrylamide gel or a 6% Nusieve gel, we measured the size of the obtained fragments and determined the number of CAG repeats since a 282 basepair fragment corresponds to 21 CAG. We previously showed that the number of CAG repeats within the AR gene exon 1 in 23 families with complete or partial androgen insensitivity syndrome was 19 +/- 4. By this method, we detected heterozygosity in 50% of the mothers. We present here 2 exclusion prenatal diagnoses using exon 1 polymorphism of the AR gene. Family A presented a boy with a severe form of partial androgen insensitivity syndrome. The mother had 2 uncles with ambiguous genitalia. In family B, the affected child had a complete androgen insensitivity syndrome. In both families, analysis of the AR gene exon 1 polymorphism of the trophoblastic DNA showed the presence of the normal maternal X chromosome. The parents decided to carry on the gestation. In family A, the newborn had normal male external genitalia. In family B, sonography confirmed the presence of normal male external genitalia. These data suggest that exon 1 polymorphism of the AR gene could be prenatally used to predict androgen insensitivity syndrome.     

Dicentric Y chromosome in a patient with gonadal dysgenesis and seminoma

Summary A male patient with ambiguous external genitalia developed a seminoma in the left inguinal region; his internal genitalia included a streak gonad on the right and a small uterus.Cytogenetic studies demonstrated a dicentric Y chromosome with unstable behavior during cell division, which resulted in 45,X/46,X,dic(Y)/47,X,dic(Y),dic(Y) mosaicism.Immunogenetic studies allowed the identification of the male-determining H-Y antigen on both leukocytes and red cells of the patient.The significance of these results is discussed with respect to recent data on the genetic control of H-Y antigen.This work was supported in part by CNR Centro di studio per l'Immunogenetica e l'Istocompatibilità