Ring Y chromosome without mosaicism

A 53-year-old man with a short stocky build, mild mental retardation, gynecomastia and hypogonadism was found to have a small ring Y chromosome unassociated with mosaicism. The ring Y was represented by a minute portion of chromatin or sometimes paired dots which were no larger than the short arm of the normally expected Y. No brightly fluorescent segment of the ring Y was present nor was it observed elsewhere in the karyotype. A primary medical problem was severe osteoarthritis, necessitating bilateral hip arthroplasties. Plasma testosterone was markedly decreased and plasma gonadotropins were increased. Potency was improved following testosterone injections. We conclude that genes responsible for testicular differentiation, maleness and possibly height are located close to the centromere of the Y chromosome, possibly on both the short and long arm. We also conclude that multiple genes are required for a fully developed male phenotype and apparently some of these genes were deleted or not expressed in this patient.     

Labyrinthine anomalies in trisomy 13 mosaicism

The temporal bone histopathology of a 2-month-old male with a bilateral cleft palate, cleft lip and polydactylia due to trisomy 13 mosaicism was studied. Anomalies in the ear involved a partial absence of the superior semicircular canal, an abnormally wide lateral semicircular canal, underdeveloped cochlear coils, an abnormally broad modiolus, an undeveloped organ of Corti and an underdeveloped basilar membrane in the basal turn of the cochlea, an unusually wide cochlear aqueduct, and deformed stapedial crura.     

Cortical dysgenesis in a patient with Turner mosaicism

BACKGROUND: Although there is increasing interest in the use of glycolic acid in the treatment of photoaged skin, to our knowledge, no controlled study has been done to assess the efficacy or the mode of this agent. OBJECTIVE: The purpose of this study was to determine whether 50% glycolic acid can improve photoaged skin and to study the histological basis for this improvement. METHODS: Forty-one volunteers were recruited into this double-blind vehicle-controlled study. Glycolic acid (50%) or vehicle was applied topically for 5 minutes to one side of the face, forearms, and hands, once weekly for 4 weeks. Punch biopsies were taken at pretherapy and at 5 weeks for histologic study. RESULTS: Significant improvement noted included decrease in rough texture and fine wrinkling, fewer solar keratoses, and a slight lightening of solar lentigines. Histology showed thinning of the stratum corneum, granular layer enhancement, and epidermal thickening. Some specimens showed an increase in collagen thickness in the dermis. CONCLUSION: The results of this study demonstrate that the application of 50% glycolic acid peels improves mild photoaging of the skin.     

Sertoli-Leydig cell tumour complicated by X chromosomal mosaicism

We describe a case of well-differentiated Sertoli-Leydig cell tumour (SLCT) of the ovary. A 48-year-old Japanese woman had had symptoms of virilization, i.e. alopecia and facial hair, for 8 years. Although the patient had given birth to three normal children, laboratory investigations revealed an elevated serum level of free testosterone and tripartite mosaicism (45X/46XX/47XXX). Computed tomography and magnetic resonance imaging revealed a tumour of the left ovary. After oophorectomy, the serum level of free testosterone returned to the normal range and symptoms of virilization resolved. To our knowledge, this is the first reported case of a patient with SLCT who had tripartite mosaicism and had given birth to normal children. Although the aetiology of SLCT is not known, we believe that SLCT is associated with sex chromosomal abnormalities at least in some cases.     

Three cases of mosaicism for balanced reciprocal translocations

Platelet-specific alloantigen systems are located on glycoproteins expressed at the surface of platelet membrane. These di-allelic systems are due to an amino acid substitution. An official nomenclature was adopted in 1990 by the Working Party on Platelet Serology ICST/ISBT which defined the following rules: (1) platelet-specific antigen systems are called HPA for "Human Platelet Antigens"; (2) they are numbered chronologically according to the date of publication; (3) the most frequent allele is designated by the letter a and the less frequent by the letter b (i.e., HPA-1a 1b). Since the introduction of molecular biology techniques, the nomenclature has become insufficiently precise and an adjustment will probably be required in a near future.     

Balanced reciprocal translocation mosaicism associated with an abnormal phenotype

Balanced reciprocal translocation mosaicism is rarely reported in humans. Only two previous cases have been associated with an abnormal phenotype. We report on a third case of apparently balanced reciprocal translocation mosaicism associated with an abnormal phenotype, largely different from those reported previously. Since low levels of mosaicism may not be detected in routine cytogenetic analyses, balanced reciprocal translocation mosaicism may be associated with an abnormal phenotype more often than has been recognized to date.     

Somatic mosaicism in a patient with neurofibromatosis type 1

Using loss of heterozygosity analysis, a method designed to detect moderate to large gene deletions, we have identified a new-mutation neurofibromatosis type 1 (NF1) patient who is somatically mosaic for a large maternally derived deletion in the NF1 gene region. The deletion extends at least from exon 4 near the 5' end of the gene to intron 39 near the 3' end. The gene-coding region is, therefore, mostly or entirely deleted, encompassing a loss of > or = 100 kb. We hypothesize that the deletion occurred at a relatively early developmental timepoint, since signs of NF1 in this patient are not confined to a specific body region, as seen in "segmental" NF, and since both mesodermally and ectodermally derived cells are affected. This report provides the first molecular evidence of somatic mosaicism in NF1 and, taken together with a recent report of germ-line mosaicism in NF1, adds credence to the concept that mosaicism plays an important role in phenotypic and genetic aspects of NF1 and may even be a relatively common phenomenon.     

Turner's syndrome--case report of a female patient with chromosome mosaicism

A 45-year old woman with the typical Turner's phenotype (short stature, short and broad neck, shield chest and low hairline) and signs of ovarian failure started at the age of 37 with menopause at the age of 44, is presented. The cytogenetic analysis showed the presence of three different cell lines with 45,X, 46,XX and 47,XXX karyotypes. It is a rare type of mosaicism, combining Turner's and triple-X syndrome. Interestingly, the became pregnant and gave birth to a healthy child. Second pregnancy resulted in a miscarriage in the first trimester.     

Confined placental mosaicism for trisomy 8 and intra-uterine growth retardation

This report describes a case of apparent confined placental mosaicism for trisomy 8 in a pregnancy which produced a male infant with intra-uterine growth retardation. Postnatal cytogenetic and molecular studies were consistent with biparental disomy 8. Postnatally, the infant experienced a period of rapid catch-up growth and exhibited no clinical features of trisomy 8 mosaicism. His development was age appropriate.     

Origin of nondisjunction in trisomy 8 and trisomy 8 mosaicism

OBJECTIVES: This study explores reactions to low-level chemical challenge, aiming at the development of test procedures for assessing individual sensitivity to smells and chemicals. METHODS: Subjects with symptoms and neuropsychological test results compatible with toxic encephalopathy type 2A (TE-2A) and 2B (TE-2B) and unexposed referents (N=12 in each group) were challenged in an exposure chamber. Toluene exposure was started at 11 mg/m3, and it followed a geometric progression scale with a ratio of 2, until reaching 180 mg/m3. In a counterbalanced design, the subjects were similarly exposed to n-butyl acetate starting at a concentration of 14 mg/m3 and increasing to 228 mg/m3. At each exposure level, smell intensity was measured on a 7-step category scale. Mucous membrane irritation and annoyance reactions were rated on visual analogue scales. RESULTS: Both TE groups showed high sensitivity to the low-level solvent challenge, which provoked immediate annoyance and fatigue reactions. In particular the TE-2B group related smell intensity to various annoyance dimensions during exposure to n-butyl acetate, a pattern not observed during toluene exposure. The reference group clearly separated smell intensity and annoyance reactions in both exposure conditions. CONCLUSIONS: The reaction of the TE cases suggests that chemical sensitivity can be distinguished from normal annoyance reactions by the inability to differentiate between smell intensity and an experience of irritation from mucous membranes in air concentrations well below the trigeminal irritation threshold level. Fatigue coreactivity in challenges to single substances below the neurotoxic level may also be important.     

Pathogenetics of 45,X/46,XY gonadal mosaicism

Five patients with 45,X/46,XY mosaicism ranging from 8% to 66% of 46, XY lymphocytes in the peripheral blood were studied. Their age when chromosome studies were performed ranged from a few days to 37 yr. The phenotypic presentations were two females with gonadal dysgenesis and Turner syndrome features (cases 1 and 2), two males with ambiguous genitalia and mixed gonadal dysgenesis (cases 3 and 4), and an infertile male with an atrophic testis (case 5). Fluorescence in situ hybridization (FISH) using dual-color X and Y probes on paraffin-embedded sections of the gonads was performed to assess mosaicism. A mosaic cell line with a Y chromosome was present in the streak ovary, dysgenetic gonad, and testis. In the mixed gonadal dysgenesis cases (cases 3 and 4), the testis had a higher percentage (greater than two fold) of XY cells than the ovary had. However, the highest ratio of cells with a Y chromosome was in the atrophic testis of the infertile male (case 5). The distribution of mosaic clones in the different gonadal cell types was examined. Both females (cases 1 and 2) with dysgenetic gonads had scant ovarian stroma and nests of Leydig or hilus cells. In FISH studies, the coelomic epithelial cells were predominantly 46,XY; in comparison, the Leydig and hilus cells had a lower percentage and the ovarian stroma the least number of cells with a Y signal. A mixed gonadal dysgenesis case (case 3) possessed a right testis with an XY complement in approximately 21% of Sertoli cells and approximately 14% of Leydig cells. The infertile male had an atrophic testis with interstitial hyperplasia (case 5). His testis contained Sertoli cells but no evidence of spermatogenesis. FISH detected a Y signal in about 50-60% of the Sertoli and Leydig cells.     

Identification of mosaicism in Prader-Willi syndrome using fluorescent in situ hybridization

Anti-rabbit 64 kDa oviductin (named Development Promoting Factor-1, DPF-1) antibody could inhibit totally the early development of mouse fertilised eggs cultured in the conditioned medium derived from the rabbit oviduct mucosa epithelial cells, revealed that DPF-1 synthesized and secreted from rabbit oviduct mucosa has a function to overcome the developmental block of early mouse embryos. It seems that DPF-1 consists of a group of polypeptide isoforms, since its isoelectric points are ranging from 7.2 to 8.1 (Fig. 3). The synthesis and secretion of DPF-1 was not dependent on either 17 beta-estradiol or progesterone (Fig. 7), it can pass through zona pellucida easily and associate tightly with the early embryonic cell membrane (Fig. 6). By using Western blotting method, we found that DPF-1 was not appeared in the tissues of liver, heart, lung, spleen, uterus, ovary, small intestine, skeleton muscle and brain, but in that of oviduct (Fig. 4): some DPF-1 homologous molecules were also revealed in the oviduct tissues of mouse and golden hamster, their apparent molecular weights were 32 kDa, 72 kDa in mouse, and 49 kDa, 68 kDa in golden hamster (Fig. 5). Results obtained from the in vivo anti-fertility experiment, namely to analyse the anti-fertility effect in adult female mice after active immunization with DPF-1, showed that the fertility decreased significantly as compared to those of controls (p < 0.01) (Table 1). DPF-1 and its in vivo "loss of function" evidence we obtained will encourage us to study the mechanism of DPF-1 in overcoming the developmental block of early embryos, and its role in transition from maternal to embryonic control of early development.     

The oro-facial manifestations of trisomy 8 mosaicism: a case report

The malformations commonly found in fetuses of diabetic mothers occur before the 7th week of pregnancy, when fetal nutritional needs are met largely by the yolk sac. The diabetic milieu has been hypothesized to cause a disruption in the metabolism of arachidonic acid and phosphatidylinositol turnover, leading to a reduction in prostaglandin levels. In this study we evaluated how the diabetic milieu affects yolk-sac prostaglandin levels. We used ultrasound to characterize and guide aspiration of the yolk sacs of eight diabetic and 12 healthy women prior to elective abortion. In addition, we studied the yolk sacs of two healthy women in whom pregnancy termination was carried out by hysterectomy. All fetuses were between 8 and 10 weeks gestational age at the time of pregnancy termination. The yolk-sac prostaglandin E2 levels were measured using radioimmunoassay. We found that the yolk-sac diameters of diabetic women were 1.2 mm larger than those of normal women. Furthermore, the mean prostaglandin E2 level in healthy women was 3605 pg/ml, whereas prostaglandin was undetected in all the yolk sacs of diabetic women (p < 0.001). While this study suggests that defective yolk-sac metabolism of prostaglandins is one of the mechanisms responsible for diabetic embryopathy, further research is necessary to place yolk-sac enlargement and the role of prostaglandins in perspective.     

The outcome of pregnancies with confined placental chromosome mosaicism in cytotrophoblast cells

Cytogenetic findings and outcome of pregnancy are reported in 108 cases in which confined placental mosaicism (CPM, n = 101) or generalized mosaicism (n = 7) was found at or after first-trimester chorionic villus sampling. In all samples, a (semi)direct cytogenetic analysis of cytotrophoblast cells was performed. Two pregnancies with CPM ended in a spontaneous abortion before 28 weeks (1.9 per cent). In 15 cases the pregnancy was terminated: eight cases were shown to be examples of CPM; seven cases can be considered as examples of generalized mosaicism. A normal cytogenetic result was obtained after follow-up amniocentesis in 88 of the remaining 91 cases. In three cases, no amniocentesis was performed but confirmation of a normal karyotype was obtained in other cells. One of the 91 pregnancies was nevertheless terminated for psychosocial reasons. One child died perinatally and another on the seventh day after birth. The birth weight is known for 89 children; the curve shows a normal distribution. In 11 of these children (12.3 per cent), the birth weight was found to be below the tenth centile. The outcome in a subgroup of eight pregnancies with CPM and involvement of chromosome 13, 16, or 22, however, revealed two fetal losses and four children with a birth weight below the tenth centile (75 per cent).     

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

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

Familial ring (19) chromosome mosaicism: case report and review

Ring (19) chromosomal mosaicism has been identified in a 14-month-old girl referred for cytogenetic evaluation due to microcephaly and developmental delay with autistic-like mannerisms. An analysis of her peripheral blood lymphocytes showed a 46,XX,r(19) cell line in 119/121 of cells examined. Of the two remaining cells, one had a normal female chromosome complement and the other showed loss of one of the chromosome 19 homologs. Further analysis by fluorescence in situ hybridization using an all human telomere probe showed the presence of a single hybridization signal on the r(19) chromosome. Subsequent cytogenetic characterization of cells derived from the patient's phenotypically normal mother also demonstrated the presence of a ring 19 chromosome in 4/100 cells. The remaining cells had a normal female chromosome complement. These findings represent the first reported case of familial ring 19 mosaicism. The cytogenetic and clinical findings in these two individuals are discussed in relation to six previously reported cases of de novo ring chromosome 19 mosaicism.     

Trisomy 1 mosaicism only detected on a direct chromosome preparation in a neonate

A patient is described with trisomy 1 mosaicism which was discovered on 24-h culture of a neonatal blood sample, but was not detectable on subsequent 48- and 72-h cultures. This result complements other recent reports and has important implications for the detection of mosaicism in neonates.     

Relationship between the mosaicism of myocardial damage and the metabolic heterogeneity of myocardiocytes

Uridine-3H (2 muCi/g of body weight) was injected intraperitoneally to albino mice; this was followed (in one hour) by isopropylnoradrenaline (0.1 mg/g of body weight). The animals were sacrified in 10 minutes. Autoradiographic analysis and polarisation-microscopic study of the myocardial section showed that myokardiocytes with a lower level of the RNA synthesis were to the contracture lesions.