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.

A case with Waardenburg syndrome presenting with two separate translocations--one reciprocal and one complex.

A 2-month-old Turkish male with Waardenburg syndrome who has two de novo translocations is described. The translocations are a reciprocal translocation between chromosomes 1 and 8, and a more complex translocation involving chromosomes 4 and 7.

The predictive value of findings of the common aneuploidies, trisomies 13, 18 and 21, and numerical sex chromosome abnormalities at CVS: experience from the ACC U.K. Collaborative Study. Association of Clinical Cytogeneticists Prenatal Diagnosis Working Party.

We report 611 non-mosaic and 91 mosaic findings of trisomies 13, 18 and 21, and numerical sex chromosome abnormalities in a series of 20,527 CVS, in the Association of Clinical Cytogeneticists U.K. Collaborative Study, the majority with analysis of both direct preparations and cultured cells. No false-positive results were encountered among the 611 non-mosaic cases, making these findings a very reliable indicator of the fetal karyotype. One false-negative case was reported. In contrast, the 91 mosaic abnormalities were unreliable predictors of fetal abnormality. Many were associated with normal outcomes, but a significant proportion of cases of each individual aneuploidy proved genuine. Mosaicism for 45,X, and trisomies 13 and 18 was disproportionately common. 17 of the mosaic cases showed complete discordance between the karyotype from direct preparations and that from cultured cells. All would have resulted in either a false-positive or a false-negative finding if only one technique had been used. Based on our experience, and that of others, we believe that the highest level of predictive accuracy using CVS can only be achieved if both direct preparation and cell culture are performed. In addition, we continue to recommend that all pregnancies demonstrating mosaicism for these aneuploidies at CVS undergo amniocentesis or fetal blood sampling to differentiate between confined placental mosaicism and true fetal karyotypic abnormality.

Two years' prospective experience using fluorescence in situ hybridization on uncultured amniotic fluid cells for rapid prenatal diagnosis of common chromosomal aneuploidies.

A probe was generated from the YAC clone 831B9 that was suitable for the prenatal detection of trisomy 21 using fluorescence in situ hybridization (FISH). This probe was initially tested on a series of 650 unselected amniotic fluid samples prior to the karyotype being available. 630 were correctly identified as having two copies and 13 samples were correctly scored as having three copies of chromosome 21. Seven samples failed to produce a result. A trial was then initiated, reporting to clinicians the interphase FISH results before cytogenetic analysis had been performed. During the first 18 months of this trial 1504 samples were tested: 1467 were correctly identified as disomic and 35 samples were correctly scored as trisomic for chromosome 21. Two samples failed to produce a result. A chromosome 18 specific probe (LI.84) was employed where there was a relevant clinical indication (181 samples) and 10 samples were correctly scored as having three copies of chromosome 18. Thus, this approach appears to be reliable and is popular with both clinicians and patients due to the speed of the result. However, it does not replace chromosomal analysis on cultured cells, which detected a range of abnormalities besides the trisomies and triploidies detected by FISH.

Trends in prenatal diagnosis of Down syndrome and other autosomal trisomies in Scotland 1990 to 1994, with associated cytogenetic and epidemiological findings.

The present report summarizes findings on 670 cases of autosomal trisomy diagnosed in Scotland, with actual or expected dates of delivery in 1990 to 1994 inclusive. Cases were notified by cytogenetic service laboratories. There were 277 prenatal and 369 postnatal diagnoses and 24 spontaneous losses. Excluding the latter, numbers diagnosed with trisomy 21, trisomy 18, trisomy 13, and other trisomies were, respectively, 470 (72.8%), 108 (16.7%), 36 (5.6%), and 32 (5.0%). Estimated maternal age-specific birth rates for trisomy 21 were close to published values from other jurisdictions. However, comparisons with a clinically based national register of congenital anomalies suggested that 3-4% of Down syndrome births were never karyotyped, most being early neonatal deaths. There was a striking increase over the period in the proportion of cases detected prenatally, associated with increased maternal serum screening in mothers <35 years old. Over the 3 final years (1992-1994), prenatal screening followed by elective termination was estimated to reduce the birth rate in trisomy 21 by 24% in mothers aged <35 years, by 57% in older mothers, and by 35% in all mothers. The crude incidence per 1,000 births fell from 1.08 in 1990-1991 to 0.77 in 1992-1994, in spite of an upward shift in the overall maternal age distribution. For trisomies 18 and 13, the estimated overall reductions in the birth rate over the whole 5-year period were respectively, 26 and 17%. In free trisomy 18, there was a significant reduction in the sex ratio (male/female) to 0.65, in line with earlier studies.

Molecular cytogenetic characterization of a critical region in bands 7q35-q36 commonly deleted in malignant myeloid disorders.

Loss of chromosome 7 (-7) or deletion of the long arm (7q-) are recurring chromosome abnormalities in myeloid leukemias. The association of -7/7q- with myeloid leukemia suggests that these regions contain novel tumor suppressor gene(s), whose loss of function contribute to leukemic transformation or tumor progression. Based on chromosome banding analysis, two critical regions have been identified, one in band q22 and another in bands q32-q35. Presently there are no data available on the molecular delineation of the distal critical region. In this study we analyzed bone marrow and blood samples from 13 patients with myeloid leukemia (de novo myelodysplastic syndrome [MDS], n = 3; de novo acute myeloid leukemia [AML], n = 9; therapy-related (t-) AML, n = 1) which, on chromosome banding analysis, exhibited deletions (n = 12) or in one case a balanced translocation involving bands 7q31-qter using fluorescence in situ hybridization (FISH). As probes we used representative clones from a contig map of yeast artificial chromosome (YAC) clones that spans chromosome bands 7q31.1-qter. In the 12 cases with loss of 7q material, we identified a commonly deleted region of approximately 4 to 5 megabasepairs in size encompassing the distal part of 7q35 and the proximal part of 7q36. Furthermore, the breakpoint of the reciprocal translocation from the patient with t-AML was localized to a 1,300-kb sized YAC clone that maps to the proximal boundary of the commonly deleted region. Interestingly, in this case both homologs of chromosome 7 were affected: one was lost (-7) and the second exhibited the t(7q35). The identification and delineation of translocation and deletion breakpoints provides the first step toward the identification of the gene(s) involved in the pathogenesis of 7q35-q36 aberrations in myeloid disorders.

Effects of lacrimal drainage occlusion with nondissolvable intracanalicular plugs on hydrogel contact lens wear.

PURPOSE: To investigate effects of lacrimal drainage occlusion with intracanalicular silicone plugs in hydrogel lens wearers with the symptom of dryness. Effects of rewetting drops in combination with the plugs were also evaluated. METHODS: A 6-week, prospective, double masked, placebo-controlled study design was followed. Thirty-five patients (26 females and 9 males) were entered into the study based on specific symptoms and signs of dry eye with hydrogel lens wear. Baseline symptoms, noninvasive prelens tear film break-up time, lens water content, fluorescein, and rose bengal staining were recorded. Herrick Lacrimal Plugs were inserted into both canaliculi of one previously randomized eye by an independent investigator. The fellow eye was manipulated in a sham procedure. Symptoms and signs were followed over 4 weeks. Nonpreserved rewetting drops were used in both eyes during the 5th week. Symptoms and signs were again followed. RESULTS: Symptoms improved more significantly in the plugged eye than the control eye after insertion of the plugs, and again after use of the drops. This improvement diminished in some of the patients. Prelens tear film break-up time was not significantly changed. Water content of all lenses combined increased only in the plugged eye with the use of drops. Fluorescein staining decreased significantly in the plugged eye. Rose bengal staining showed a slight decrease in the plugged eye. CONCLUSIONS: Intracanalicular silicone plugs offer improvement of symptoms and signs of dryness in this population. There seems to be some decrease in improvement of symptoms with the plugs over time. Concurrent use of rewetting drops increases the benefits.

Prenatal diagnosis in the United Kingdom--an overview.

Prenatal diagnosis is now a well-established part of health care in the UK. Cytogenetic or molecular diagnostic analysis following amniocentesis, chorionic villus sampling or cordocentesis is in routine practice and identification of 'at risk' pregnancies using biochemical screening or ultrasound is widespread. Professional guidelines have been established covering both sampling procedures and diagnostic testing, and legislation is in place regarding termination of pregnancy and pre-implantation diagnosis. The close liaison of the various groups of professionals involved has led to well-developed prenatal diagnostic and screening services within the UK. These links have been the major contributory factor to the current state of prenatal diagnosis and have been of great benefit to patients undergoing prenatal testing.

Swelling of collagen intracanalicular implants.

BACKGROUND: Absorbable intracanalicular collagen implants are used to attempt to determine if permanent closure of the tear drainage system will diminish or alleviate the signs and symptoms of dryness. The rate of swelling of the collagen implants was measured in vitro in this study. METHODS: Collagen implants were submersed in saline, Refresh Plus artificial tears or Tobrex antibiotic solution on a hanging drop microscope slide. The diameter of the collagen rod was measured over time using videotaping and image processing. RESULTS: The 0.3- and 0.4-mm diameter collagen implants swelled approximately 55% to 65% in Unisol 4 Preservative Free saline and Refresh Plus artificial tear solution, with the majority of the swelling occurring over the first 30 minutes. The 0.4-mm diameter implants took slightly longer to reach the fully swollen state than did the 0.3-mm implants. They swelled somewhat less in Tobrex Ophthalmic Solution. CONCLUSIONS: Collagen implants swell approximately 60%, with the majority of the swelling occurring in the first 30 minutes. Thus, it will take approximately 30 minutes after insertion of the implants for the full occlusive effect to occur.

Long-term culture of primary breast cancer in defined medium.

Over a period of 6 1/2 years between January 1986 and May 1992, 135 unselected primary breast cancers were cultured and of these 10 developed into cell lines. Six of the lines grew in defined serum-free medium, while the other four required supplementation with 0.5% fetal calf serum. Two of the lines are from the same breast, being derived from a local excision specimen and from a mastectomy specimen 12 months later. In addition, 12 lymph nodes containing metastatic breast cancer were cultured; one of these cultures became permanent in a defined serum-free medium. Oestrogen receptor (ER) status was negative in all but one of the tumours which grew successfully, and even in this case the derived cell line is ER negative. The epithelial nature of the lines has been confirmed by immunocytochemistry and by electron microscopy (EM), while their malignant nature is shown by morphology, unattached growth, chromosome analysis, and, in the case of the line from a lymph node metastasis, the absence of any benign source of epithelial cells.

Uniparental isodisomy for chromosome 16 in a growth-retarded infant with congenital heart disease.

We report a growth-retarded infant with congenital heart disease and maternal isodisomy for chromosome 16. Non-mosaic trisomy 16 was detected at mid-trimester chorionic villus sampling, performed because biochemical screening indicated an increased Down's syndrome risk. Further karyotyping analysis of the placenta, after delivery, showed a 50 per cent mosaic trisomy 16. The infant had an atrioventricular (A-V) canal defect, scoliosis, and several minor dysmorphic features. Although uniparental disomy for chromosome 16 has been reported previously, to our knowledge this is the first case of uniparental isodisomy for chromosome 16 which has been investigated with multiple DNA probes.

Midtrimester chorionic villus sampling: an alternative approach?

OBJECTIVE: Our purpose was to audit midtrimester chorionic villus sampling after a positive maternal serum screening test for autosomal trisomy. STUDY DESIGN: From January 1990 until July 1993 chorionic villus sampling was offered to all screened positive women. RESULTS: Five hundred fifty-one mothers had chorionic villus sampling. The mean age was 31.7 years. The mean gestational age was 18.2 weeks. The mean time for direct karyotyping was 4.4 days and for culture results 20.2 days. Results were obtained in 99.6% of samples: direct plus culture results in 94%, direct results alone in 2.3%, and culture results alone in 3.3%. Fourteen pregnancies had abnormal karyotypes. There were five cases of placental mosaicism and one false-positive result. The loss rate was 0.4%. CONCLUSION: Midtrimester chorionic villus sampling, which is easier to perform than cordocentesis, provides a rapid and reliable karyotype. The complication rate is comparable to that of other invasive procedures.

Congenital ocular defects associated with an abnormality of the human chromosome 1: trisomy 1q32-qter.

This article describes the detailed ocular pathology found in a premature neonate, born at 34 weeks, with multiple congenital anomalies resulting from de novo trisomy 1q32-qter. The ocular defects include goniodysgenesis, persistent tunica vasculosa lentis and hyaloid vessels, hypopigmentation of the posterior iris epithelium, ectopia of the ciliary processes, and abnormal insertion of the ciliary muscle and cataract. This is the first report of the detailed ocular pathology in a case of trisomy 1q and is also unusual in that the chromosomal defect has apparently arisen de novo in the proband.

A synopsis of extended-wear lenses and lens care regimens.

The clinical properties of hydrogel and rigid gas-permeable contact lenses for extended wear are examined, with emphasis on oxygen permeability and transmissibility, so that clinicians may select lenses likely to minimize corneal edema or may predict the amount of edema likely with a given lens. Lens deposit formation and related problems are also described, as are lens care systems, particularly their limitations with respect to preventing infections. The advantages, disadvantages, and limitations of lens cleaners are discussed, and recommendations for use are provided.