Sex chromosome loss, micronuclei, sister chromatid exchange and aging: a study including 16 centenarians.

In the present study we analysed the possible effect of age, sex and smoking on the mean values of micronucleus (MN) and sister chromatid exchange (SCE) frequencies on peripheral blood obtained from 38 subjects ranging in age from 16 to 63 years and 16 centenarians. The mean number of binucleated cells with micronuclei varied in function of age and sex (as demonstrated by the analysis of covariance (F=13.13; P<0.001), particularly evident was the increment observed in women with increasing age (interaction age/sex: F=5.53; P<0.05). Smoking habits had no effects on MN frequency (F=0.36; P>0.05). Sex (F=4.18; P<0.05) and smoking habits (F=14.64; P<0.001) influenced significantly SCE per cell frequencies, but age had no effects on them (F=2.45; P>0.05). The age-associated increase of sex chromosome loss was studied using fluorescence in situ hybridisation (FISH) on interphase nuclei. The loss of Y signals was observed in approximately 10% of interphase cells from the centenarians males, that is six times more often than in the younger control men (approximately 1.6%). The frequency of X signal loss (approximately 1.7%) in young women was similar to that observed in male controls of the same age but the incidence of the X chromosome aneuploidy in centenarian females was appreciably higher (approximately 22%) than that found for the Y chromosome in males. These results were correlated with the data on MN formation and a positive correlation between the percentage of aneuploid cells (FISH) and MN values was observed (r=0.50; P<0.05).

Recombination in the pseudoautosomal region in a 47,XYY male.

Males with a 47,XYY karyotype generally have chromosomally normal children, despite the high theoretical risk of aneuploidy. Studies of sperm karyotypes or FISH analysis of sperm have demonstrated that the majority of sperm are chromosomally normal in 47,XYY men. There have been a number of meiotic studies of XYY males attempting to determine whether the additional Y chromosome is eliminated during spermatogenesis, with conflicting results regarding the pairing of the sex chromosomes and the presence of an additional Y. We analyzed recombination in the pseudoautosomal region of the XY bivalent to determine whether this is perturbed in a 47,XYY male. A recombination frequency similar to normal 46,XY men would indicate normal pairing within the XY bivalent, whereas a significantly altered frequency would suggest other types of pairing such as a YY bivalent or an XYY trivalent. Two DNA markers, STS/STS pseudogene and DXYS15, were typed in sperm from a heterozygous 47,XYY male. Individual sperm (23,X or Y) were isolated into PCR tubes using a FACStarPlus flow cytometer. Hemi-nested PCR analysis of the two DNA markers was performed to determine the frequency of recombination. A total of 108 sperm was typed with a 38% recombination frequency between the two DNA markers. This is very similar to the frequency of 38.3% that we have observed in 329 sperm from a normal 46,XY male. Thus our results suggest that XY pairing and recombination occur normally in this 47,XYY male. This could occur by the production of an XY bivalent and Y univalent (which is then lost in most cells) or by loss of the additional Y chromosome in some primitive germ cells or spermatogonia and a proliferative advantage of the normal XY cells.

A reinvestigation of non-disjunction resulting in 47, XXY males of paternal origin.

We have used polymorphisms within the Xp/Yp pseudoautosomal region (PAR 1) to determine the frequency and location of recombination in 80 paternally derived 47, XXY males. Of 64 informative results, there were 10 single cross-overs, one double cross-over and 53 without a cross-over. Therefore 2/3 of 47, XXY males of paternal origin result from meiosis in which the X and Y chromosomes fail to recombine. This failure was not associated with the presence of an increase in recombination in the smaller Xq/Yq pseudoautosomal region (PAR 2) or with the presence of microdeletions within PAR 1.

Case of XXXXY syndrome. Development throughout adolescence and endocrine aspects.

49,XXXXY syndrome is a very rare condition that is associated with a considerable more severe phenotype than classic 47,XXY Klinefelter syndrome. We present a patient with 49,XXXXY syndrome, who was first presented to an endocrinological unit at the age of 12.5 years with prepubertal genitalia. He was then lost from follow-up and showed clear clinical and biochemical signs of hypergonadotropic hypogonadism when presenting again at the age of 16 years. The patient was started on testosterone replacement therapy. This case is reported to underline the need for thorough endocrinological follow-up examinations in males with X polysomies.

Sex chromosome aneuploidies in sperm of 47,XYY men.

The sex chromosomal equipment in 26,675 sperm of 47,XYY males was analyzed. A total of 5.78% of the nuclei exhibited sex chromosome hyperhaploidy. Six studies have analyzed the sperm of 10 XYY patients and, although these studies indicated some degree of elimination of the extra Y chromosome during spermatogenesis, a certain percentage of XYY germinal cells may also be able to achieve meiosis and produce sperm with gonosomal disomies. All these studies show an increased incidence of gonosomal aneuploidies in sperm, but there are significant discrepancies concerning the extent of these abnormalities. The global frequencies of sperm with an abnormal number of sex chromosomes ranged from 0.578 to 13.91%, depending on the patients. There are several explanations for these discrepancies: differences attributed to fluorescence in situ hybridization methodology, the use of dual or multicolor FISH, recruitment, interindividual variations, and intraindividual variations. This study reports an additional series obtained from another XYY individual and compares and discusses the data on gonosomal hyperhaploidies in sperm of 47 XYY males using in situ hybridization analyses.

Deletion of Y chromosome involving the DAZ (deleted in azoospermia) gene in XX males.

The testicular histology and the presence or absence of 32 Y DNA loci was investigated, with a focus on the long arm of Y chromosome (Yq) interval 6, by means of a polymerase chain reaction strategy in 2 XX males. Seminiferous tubules lined by only Sertoli cells and a slight thickening of tubular walls were observed. The men showed an absence of 32 Y DNA loci. These facts suggest that severe spermatogenic impairment is caused by deletions of Yq interval 6 in XX males.

[X-linked recessive bulbospinal neuronopathy--Kennedy's syndrome]. / X-bundet recessiv bulbospinal neuronopati--Kennedys syndrom.

Kennedy's syndrome is an inherited disease which was probably first described 100 years ago. Although rare, a recent report suggests that the prevalence may show considerable regional differences. A review of 30 different names of the disease is given. Originally, the disorder was regarded as a spinal and bulbar muscular atrophy but it is now obvious that there is severe axonal degeneration, also of the sensory fibres with the pattern of a central-peripheral distal axonal neuropathy. This was also present in the two recognized cases presented here. The sensory symptoms develop slowly and it is suggested that a peripheral sprouting compensates for the loss not only of motor, but also sensory fibres. It is important to distinguish the disease from motor neuron diseases since the progression is slow and the expected life span is normal. The clinical presentation with facial palsy and perioral contraction-fasciculations is pathognomonic. However, demonstration of increased (CAG)n repeat size in the androgen receptor gene is diagnostic. A normal (CAG)n repeat size excludes the diagnosis, since the abnormal expansion is the only mutation associated with the disease. Other types of mutations in the androgen receptor gene lead to a different clinical presentation, testicular feminization.

Another observation of microphthalmia in an XX male: microphthalmia with linear skin defects syndrome without linear skin lesions.

A case of microphthalmia with Xp microdeletion is reported. The patient was a boy who showed bilateral microphthalmia with corneal opacities, hypospadias without evidence of hypogonadism, and a conduction disturbance of the heart (Wenckebach conduction). No skin lesion was discerned. High-resolution chromosome analysis revealed the karyotype of 46,X,del(X)(p22). The phenotype was considered to be microphthalmia with linear skin defects (MLS) syndrome without skin lesions. Polymerase chain reaction and fluorescence in-situ hybridization analyses revealed that the chromosome aberration resulted from an X;Y translocation: the presence of pseudoautosomal boundary Y and the sex-determining region of Y was confirmed, while Xp deletion involving the region distal to DXS1129 was ascertained. Thus the chromosome designation using the ISCN 1995 nomenclature is 46,X,der(X),t(X;Y)(p22.13;q11.2). Despite the absence of skin lesions, the Xp deletion of our patient corresponded to those of previously reported typical cases of MLS syndrome. Our observation further supports the current hypothesis that the phenotypic variation of MLS syndrome represents tissue-different X inactivation rather than different genetic effects of two contiguous genes.

Case report of a 22-week fetus with 47,XXX karyotype and multiple lower mesodermal defects.

A 22-week stillborn fetus with 47,XXX karyotype had lower mesodermal defects consisting of irregular fusion of the sacral vertebrae, anal agenesis, multicystic dysplasia of a horseshoe kidney, a single umbilical artery, dysplastic ovaries, and uterine hypoplasia. This case provides additional evidence for an association between trisomy X and genitourinary defects including lower mesodermal defects sequence.

X-linked lymphoproliferative disease: pathology and diagnosis.

X-linked lymphoproliferative disease (XLP) is a rare familial disorder resulting in selective immunodeficiency to the Epstein-Barr virus (EBV), characterized by uncontrolled proliferation of EBV-infected lymphocytes. Phenotypes of this disease are variable and include fulminant infectious mononucleosis, hypogammaglobulinemia, and malignant lymphoma. In this article, we describe a case of a previously healthy 4-year-old boy with serologic evidence of acute EBV infection who died of fulminant hepatic failure. Histopathological examination of tissue obtained postmortem showed hemophagocytosis and prominent polymorphous infiltrates associated with necrosis in the liver, spleen, and lymph nodes. Semiquantitative polymerase chain reaction (PCR) utilizing primers complementary to the EBV gene LMP2a performed on samples of liver tissue demonstrated approximately 0.6 copies of the EBV gene per cell. Immunohistochemistry demonstrated light chain restriction and PCR studies of the immunoglobulin V-D-J region revealed two strong bands, consistent with a clonal B cell proliferation. Extended family history revealed that the boy's family was followed by the XLP Registry, which was established in 1978 to follow kindreds with XLP. The genetic abnormality associated with XLP has been localized to the Xq25, allowing RFLP analysis to identify female carriers and affected boys.

An XXY sex chromosome constitution in a house musk shrew (Suncus murinus L.) with testicular hypoplasia.

An adult male house muck shrew with an XXY sex chromosome constitution was found in a laboratory-bred colony. Maternal origin of the additional X chromosome was demonstrated. The external appearance of the animal was normal, but the testes were small and displayed a high density of interstitial cells. The seminiferous tubules were narrow and contained only Sertoli cells.

Chromosome 21 detection in human oocyte fluorescence in situ hybridization: possible effect of maternal age.

PURPOSE: The purpose of this study was to evaluate, among 100 uncleaved oocytes, the incidence of numerical and structural chromosome 21 and X abnormalities and to analyze the influence of various factors, such as in vitro (IVF) indications, follicle stimulation protocols, and women's age. METHODS: We investigated 150 uncleaved oocytes from 128 patients after an IVF attempt. After cytogenetic analysis (Giemsa) 100 oocytes (66%) were selected for fluorescence in situ hybridization (FISH). Fluorescent probes for human chromosomes X and 21 were used simultaneously according to standard procedures for their hybridization and detection. RESULTS AND CONCLUSIONS: We analyzed by the FISH protocol 100 metaphase II oocytes with 22 to 25 chromosomes. Our results demonstrate a high rate of disomy for chromosome 21 in human oocytes. Among them, eight were disomic (8%) and three were nullosomic (3%) for chromosome 21. Only one disomy of chromosome X was noted. The various indications of IVF and the different folliculogenesis stimulating protocols did not seem to influence the results but suggested a correlation between the maternal age and the aneuploidy rate of chromosome 21.

Short-arm dicentric Y chromosome associated with Sertoli-cell-only tubule.

We report a case of a short-arm dicentric Y chromosome associated with Sertoli-cell-only tubule. Chromosomal analysis, using G- and C-banding techniques, revealed: 45,X/46,X psu dic(Y) (pter-->q11::q11-->pter)/46,X + mar. Staining by fluorescence in situ hybridization using a Y chromosome centromere-specific DNA probe showed two bright spots in the pseudodicentric Y chromosome and one in the marker chromosome. It is assumed that Sertoli-cell-only tubule is caused by deletion or disruption of the azoospermic factor gene located distal in Yq11.

A superfemale with primary Sjögren's syndrome which involved systemic organs.

A 52-year-old Japanese woman complicated by a sex chromosomal anomaly as a superfemale, a mosaic of XXXXX/XXXX/XXX/XX/XO, with mild mental retardation, was hospitalized for dry mouth, dry eyes, and proteinuria. The sialography of the right parotid gland showed a globular-type gland enlargement. A definite diagnosis of primary Sjögren's syndrome (SS) was made, and further examinations revealed not only typical sicca syndrome but also systemic extraglandular lymphocytic infiltration; interstitial pneumonitis, glomerular- and interstitial nephritis, superficial gastritis, thyroiditis, and a severe excitation conductive impairment of heart. We report a very rare case of superfemale with primary SS which involved systemic organs.

Turner syndrome in a mother and daughter: r(X) and fertility.

A patient with mosaic Turner syndrome and normal fertility had three documented pregnancies. She had a 45,X/46,X,r(X) karyotype and did not undergo spontaneous sexual maturation and menarche. Conception occurred while on hormone replacement therapy. Her first pregnancy ended with the birth of a normal 46,XY male, while the third pregnancy resulted in a healthy 45,X/46,X,r(X) female. A review of the literature reveals a myriad of theories to account for the variability of ovarian function in Turner syndrome, but, as yet, there are insufficient data to yield any conclusions. There appears to be an increased risk of trisomy 21 in the offspring of females with Turner syndrome.

Aggressive fibromatosis (desmoid tumor) is a monoclonal disorder.

Aggressive fibromatosis (also called deep fibromatosis or desmoid tumor) is a proliferation of cytologically benign-appearing fibrocytes, often resulting in significant functional loss. The nature of the lesion is controversial: some evidence suggests that it is a reactive process, whereas other evidence supports a neoplastic etiology. The pattern of X chromosome inactivation, using a technique based on polymerase chain reaction (PCR) amplification of a hypervariable CAG repeat region flanking Hhal restriction sites of the human androgen receptor gene, was determined in four cases in which cryopreserved tumor and adjacent normal tissue were available. All four tumors demonstrated a monoclonal pattern, while the adjacent normal tissues demonstrated a polyclonal pattern. This demonstrates that aggressive fibromatosis is proliferation of cells derived from a single clone with a growth advantage, and thus is likely a neoplastic process.

Estudio de cromatina X y Y en pacientes epilépticos / X and Y chromatin study in epileptic patients

Algunos autores han informado que las alteraciones en el número de cromosomas sexuales son más frecuentes en pacientes epilépticos. En este trabajo se estudió la cromatina X y Y en una población de pacientes epilépticos con objeto de detectar alteraciones en el número de cromosomas sexuales en ellos. Se estudiaron 608 hombres y 537 mujeres mediante la cromatina X, no encontrándose ninguna alteración en esta prueba. En 279 hombres se determinó la cromatina Y en la cual tampoco se encontraron anormalidades