Sexual and somatic determinants of the human Y chromosome: studies in a 46,XYp- phenotypic female.

A case of a 46,XYp- phenotypic female provided an opportunity to evaluate both sexual and somatic determinants for the Y chromosome. The patient had multiple stigmata of Turner syndrome, but normal stature. Laparotomy revealed a normal uterus and tubes, with 1.5 cm undifferentiated gonads. Serological tests for H-Y antigen (ostensibly the product of Y-chromosomal testis-determining genes) indicated absence of the H-Y+ phenotype normally associated with the intact Y chromosome. We conclude that genes exist on the short arm of the human Y chromosome which both suppress some of the somatic stigmata of Turner syndrome and determine normal expression of H-Y antigen and testicular differentiation of the primitive gonad. Our data are consistent with the view that H-Y genes comprise a family of testis-determinants, and that loss of a critical moiety is inconsistent with normal development of the male gonad.     

Chimerism 46,XX/46,XY in a phenotypic female

Summary A female patient is reported with lymphocyte chromosome chimerism (46,XX/46,XY). Her whole-body chimerism was confirmed in the AB0 blood group system by the presence of two different erythrycyte populations, A₁0 and 00. Normal findings were recorded at physical and gynecological examination, except for mammary hypoplasia and sterility of 7 years duration, the latter complaint being the cause for genetic examination of the patient.     

46,XX/46,XX,8p- mosaicism in a phenotypically normal female

A phenotypically normal female was found to have a chromosome 8 short arm deletion in a low percentage of the cells. The reduced proportion of monosomic cells in relationship with proband's age are discussed.     

Two further males with female karyotypes

Summary Two males with the karyotype 46,XX are reported. In both individuals, the karyotype was determined in over 400 cells from lymphocyte, skin, and testis cultures.Case 1, a man born in 1935, had a normal male appearance. The Xg blood group distribution in his family was: father Xg(a+), mother Xg(a-), and propositus xg(a-). Case 2, a boy born in 1964, had penoscrotal hypospadias, and a small penis and scrotum, but otherwise appeared normal.Results of clinical, histological, genetical and blood group investigations are given.     

Nonmosaic 46,X,r(Y) karyotype with female phenotype

Summary A nonmosaic case of ring Y chromosome is described. The patient is phenotypically female and has streak gonads. The histologic examination revealed dysgenetic seminiferous tubules in the streaks and epididymislike tubules besides them. The possibilities of the development of the phenotype and the streaks are discussed.Supported by the Scientific Research Council, Ministry of Health, Hungary, 5-12-1101-02-1/L.     

A case of female hemophilia with a 46,XXr karyotype studied with X-chromosome DNA probes

Summary A case of female hemophilia with a 46,XXr/45,X karyotype and signs of Turner syndrome, has been followed for the past 10 years. One of her brothers also has hemophilia A. A study with polymorphic DNA probes located in the Xq27-qter region has enabled us to demonstrate that the ring chromosome is of paternal origin and that the factor VIII gene region is deleted. The hemizygous state allowed expression of the hemophilia A mutation, present on the morphologically normal X chromosome, inherited from her carrier mother.     

A case of 46,XY/45,X/46,XX intersex

Summary A case of 46,XY/45,X/46,XX mosaicism in a phenotypic intersex is decribed in detail. A few relevant aspects, which emerge especially from the phenotypic and karyotypic analysis, are briefly commented upon.

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Zusammenfassung Es wird ein Fall von Mosaicismus 46,XY/45,X/46,XX beschrieben. Einige Aspekte, die aus der phänotypischen und karyotypischen Analyse des Patienten hervorgehen, sind kurz kommentiert.

     

Non mendelian female sterility in Drosophila melanogaster,further data on chromosomal contamination

Molecular Genetics and Genomics - In relation to non Mendelian female sterility, Drosophila melanogaster strains can be divided into two main classes, inducer and reactive. The genetic element...     

Non mendelian female sterility in Drosophila melanogaster, further data on chromosomal contamination

Summary In relation to non Mendelian female sterility, Drosophila melanogaster strains can be divided into two main classes, inducer and reactive. The genetic element responsible for the inducer condition (I factor) is chromosomal and may be linked to any chromosome of inducer strains. Each chromosome carrying the I factor (i ⁺ chromosome) can produce females (denoted SF ) showing more or less reduced fertility when introduced by paternal gametes into reactive oocytes. The amount of fertility reduction of SF females depends chiefly on the level of reactivity of their reactive mother i.e. on the particular state of the cytoplasm in the oocytes from which they are issued. As long as i ⁺ chromosomes are transmitted through heterozygous males with reactive originating chromosomes (r chromosomes), the I factor strictly follows Mendelian segregations. In contrast, in heterozygous i ⁺/r females, a varying proportion of r chromosomes may acquire irreversibly I factor, independently of classical genetic recombination, by a process denoted chromosomal contamination. The contaminated r chromosomes behave like i ⁺ chromosomes.The experiments reported in this paper show that chromosomal contamination is a chance event which arises independently in individual r chromosomes. r chromosomes may differ in their ability to be contaminated and there is a systematic difference between chromosomes X and 2. In addition, it is demonstrated that the efficiency of contamination increases with the level of reactivity of the mothers of SF females and therefore is closely correlated with the amount of fertility reduction of SF females.     

A 46,XY female DSD patient with bilateral gonadoblastoma, a novel SRY missense mutation combined with a WT1 KTS splice-site mutation

Patients with Disorders of Sex Development (DSD), especially those with gonadal dysgenesis and hypovirilization are at risk of developing malignant type II germ cell tumors/cancer (GCC) (seminoma/dysgerminoma and nonseminoma), with either carcinoma in situ (CIS) or gonadoblastoma (GB) as precursor lesion. In 10-15% of 46,XY gonadal dysgenesis cases (i.e., Swyer syndrome), SRY mutations, residing in the HMG (High Mobility Group) domain, are found to affect nuclear transport or binding to and bending of DNA. Frasier syndrome (FS) is characterized by gonadal dysgenesis with a high risk for development of GB as well as chronic renal failure in early adulthood, and is known to arise from a splice site mutation in intron 9 of the Wilms' tumor 1 gene (WT1). Mutations in SRY as well as WT1 can lead to diminished expression and function of SRY, resulting in sub-optimal SOX9 expression, Sertoli cell formation and subsequent lack of proper testicular development. Embryonic germ cells residing in this unfavourable micro-environment have an increased risk for malignant transformation. Here a unique case of a phenotypically normal female (age 22 years) is reported, presenting with primary amenorrhoea, later diagnosed as hypergonadotropic hypogonadism on the basis of 46,XY gonadal dygenesis with a novel missense mutation in SRY. Functional in vitro studies showed no convincing protein malfunctioning. Laparoscopic examination revealed streak ovaries and a normal, but small, uterus. Pathological examination demonstrated bilateral GB and dysgerminoma, confirmed by immunohistochemistry. Occurrence of a delayed progressive kidney failure (focal segmental glomerular sclerosis) triggered analysis of WT1, revealing a pathogenic splice-site mutation in intron 9. Analysis of the SRY gene in an additional five FS cases did not reveal any mutations. The case presented shows the importance of multi-gene based diagnosis of DSD patients, allowing early diagnosis and treatment, thus preventing putative development of an invasive cancer.