Abnormal sexual differentiation in humans.
Explore the source record for details and available documents.
Breast↗
Biomedical subjects
J L Simpson
Publications and source records attributed to J L Simpson.
Gonadal and statural determinants on the X chromosome and their relationship to in vitro studies showing prolonged cell cycles in 45,X; 46,X,del(X)(p11); 46,X,del(X)(q13); and 46,X,del(X)(q22) fibroblasts.
Correlation of clinical features with cytogenetic abnormalities for individuals showing deletions of the X short arm (Xp) or the X long arm (Xq) indicate the following: (1) both Xp and Xq are necessary to assure normal ovarian development, although (2) persisting ovarian function is not infrequently associated with either (del(X)(p11) or del(Xq)(13,21,22, or 24). (3) Ovarian determinants on Xp are localized to region Xp11, but determinants on Xq cannot be precisely localized. (4) Both Xp and Xq contain statural determinants, the former localized to region Xp21 leads to Xpter. Both cell generation time and phases of the cell cycle were studied to test the hypothesis that the short stature, intrauterine growth retardation, and high embryonic lethality of 45,X can be explained on the basis of intrinsic retardation of cell division (i.e., prolonged cell cycle). Cell generation times of four 45,X fibroblast lines were significantly longer than those of for normal diploid lines, a difference accounted for by a prolonged S phase. 46,X,del(X)(p11), 46,X,del(X)(q13), and 46,X,del(X)(q22) lines also showed increased cell generation times when compared to 46,XX lines.
Adolescent↗
Cancers of the breast and female genital system: search for recessive genetic factors through analysis of human isolate.
To investigate the importance of recessive genes in female breast and genital cancers, we have conducted investigations in the Hutterites, a highly inbred genetic isolate in North America. The homogeneous life style of this group, which lives on communal farms, also facilitates distinction between shared environmental and genetic factors. We ascertained 177 cases of cancer (all organ systems) through Canadian and United States cancer registries, field trips, and searches of death certificates. Breast cancer and endometrial cancer mortalities were those expected for 1970 United States whites, but no deaths due to squamous cervical carcinoma were ascertained in this monogamous population. Inbreeding coefficients (F) for cases were higher than means for matched controls for each of the four cases of breast cancers that occurred in younger women (less than 45 years of age), for four of five cases of endometrial cancer, and for the single cases of uterine leiomyosarcoma, dysgerminoma, and ovarian adenocarcinoma. By contrast, in cases of breast cancer that occurred in women 45 years of age or older, only four of 15 F's were above those for controls. There is a significant difference between the two breast cancer age groups with respect to the likelihood that the F of cases was higher than the F of controls (chi 2 = 6.99, p less than 0.01). However, grouping cases by type, none of the F distributions were significantly different from those of their matched controls. These preliminary genetic investigations thus conform certain concepts concerning breast and female genital cancer but also suggest the desirability of further studies to elucidate the role of genetic factors in premenopausal breast cancer.
Adult↗
Chromosome analysis of ectopic human conceptuses.
Maternal factors (e.g. salpingitis) are known to be associated with ectopic gestations; however, few studies have considered the chromosomal complements or morphologic features of ectopic conceptuses. We studied 23 ectopic conceptuses removed from fallopian tubes during surgical resection. The chromosomal complements were normal (four with 46,XY; four with 46,XX) in all cases in which an intact embryo was identified, as well as in the single case characterized by disorganized embryonic tissue. Ten of the 14 ectopic conceptuses in which only a gestational sac and placental villi were identified also show normal chromosomal complements (seven with 46,XX; three with 46,XY); in the remaining four cases, variations from the normal chromosomal complement were found (46,XX/47,XX,+9; 45,X/46,XX; 46,XX/47,XX,+mar; and 92,XXXX). The former two probably signify underlying fetal abnormalities; however, the latter two could have reflected, respectively, in vitro aberrations or tetraploidy characteristic of normal amnion. Pooled data from this study and two previous reports indicate that ectopic conceptuses probable have no higher frequency of chromosomal abnormalities than in utero conceptuses of comparable embryonic ages.
Adolescent↗
Genetic counseling and genetic services in obstetrics and gynecology: implications for educational goals and clinical practice.
Analysis of genetic counseling and antenatal diagnostic services offered by a genetics unit in a women's hospital was undertaken to identify genetic needs of the obstetrician-gynecologist. For similar reasons we tabulated findings derived from a genetic questionnaire administered routinely to obstetric registrants. Certain well-defined indications for genetic referral were identified, allowing specific educational objectives to be formulated. Potential chromosomal abnormalities constitute the most common indications for referral, particularly advance maternal age and repetitive abortions. A wide range of mendelian and polygenic/multifactorial disorders was encountered, albeit many individually rare. This suggests that the obstetrician-gynecologist should become familiar with principles of these modes of inheritance. However, educational objectives need not stress specific details of rare disorders but rather should emphasize the relatively few disorders that the obstetrician-gynecologist is likely to encounter. Realistic suggestions are offered to achieve these objectives.
Female↗
Normal fetal growth despite persistent amniotic fluid leakage after genetic amniocentesis.
Two women not only lost relatively large amounts of amniotic fluid immediately following genetic amniocentesis, but continued to lose fluid for the remainder of their pregnancies. Periodic ultrasonographic assessment confirmed normal fetal growth and presence of some amniotic fluid. Both women were delivered at term of normal offspring who showed no evidence of fetal deformations. Although amnionitis is a risk, cautious surveillance may permit continuation of pregnancies complicated by copious or persistent amniotic fluid leakage following genetic amniocentesis.
Amniocentesis↗
Ultrasonic induction of sister chromatid exchanges in human lymphocytes.
We analyzed sister chromatid exchange (SCE) frequencies as an indicator of DNA damage induced in human lymphocytes by 'real-time' ultrasound. A range of exposure times and intensities was tested in a series of blind, randomized, in vitro experiments under spatial and sonographic conditions simulating exposure of a gravid abdomen and uterus. Our studies showed small but consistent effects of ultrasound on SCE frequencies, for each experiment. Differences between matched control and exposed means were significantly different from zero. chi 2 tests for homogeneity indicated no significant differences among either the means or the total distributions of the controls, nor among each of the separate dose levels. Consequently, experiments were pooled, and chi 2 analysis indicated significant differences both among distributions and among means of SCE frequencies for controls versus exposed cells (P less than 0.001). The pooled control mean was also significantly different from each of the pooled dose means. Correcting for multiple comparisons gave identical results for the paired comparisons of means except for the 20-min level which was borderline (0.025 less than P less than 0.01). We conclude that the well-established value of clinical ultrasonography warrants its continued use; however, minimizing the numbers and lengths of exposure per patient would seem prudent, pending further information on clinical implications of our results.
Adult↗
XY gonadal dysgenesis: genetic heterogeneity based upon clinical observations, H-Y antigen status and segregation analysis.
Clinical observations and segregation analysis indicate that XY gonadal dysgenesis is characterized by genetic heterogeneity. In addition to the type inherited in X-linked recessive fashion, segregation analysis of other families suggested another type by revealing that the proportion of affected sibs did not differ from that expected on the basis of a male-limited autosomal recessive inheritance. Further heterogeneity may be deduced on the basis of coexisting campomelic dwarfism or possibly also renal parenchymal abnormalities. These observations of genetic heterogeneity must be considered when interpreting studies in which individuals with XY gonadal dysgenesis may or may not show H-Y antigen.
Alleles↗
Genetic screening for donors in artificial insemination.
Explore the source record for details and available documents.
Genetic Testing↗
Parental chromosomal rearrangements associated with repetitive spontaneous abortions.
Parental chromosomal rearrangements represent a well-established cause of repetitive spontaneous abortions. However, the frequent of parental translocations varies widely in reported series, suggesting differences in ascertainment. For this reason a sample of individuals (120 women, 104 men) who had experienced spontaneous abortions but neither stillborn nor anomalous liveborn infants was investigated. Only one translocation was detected (0.4% of individuals). The relatively low frequency of translocations in this series of probably a reflection of not only lack of coexisting stillborn or anomalous infants but also the referral pattern in this unit that facilitates routine analysis of all couples experiencing repetitive abortions. In addition, one women showed a pericentric inversion.
Abortion, Habitual↗
Antenatal diagnosis of cytogenetic abnormalities.
Explore the source record for details and available documents.
Abortion, Spontaneous↗
Repeated suboptimal pregnancy outcome.
Explore the source record for details and available documents.
Abortifacient Agents↗
Genetic amniocentesis in twin gestations.
Among 1,613 women studied with routine ultrasonography prior to genetic amniocentesis at Northwestern University Medical School, 25 of 26 multiple gestations were detected. Sampling of fluid from both amniotic sacs was requested by 20 women with twin gestations in which both fetuses were ultrasonographically determined to be viable and of normal size. Fluid was obtained successfully from both amniotic sacs in 19 of 20 cases. The conclusions are that (1) twin gestations can be reliably detected by the use of routine ultrasonography, (2) both amniotic sacs can usually be sampled, and (3) the complication rate appears to be minimal to the patient and the fetuses, although the sample size is still small.
Amniocentesis↗
Heritable aspects of endometriosis. I. Genetic studies.
Systematic genetic studies in endometriosis apparently have not been conducted; therefore, we studied 123 patients with histologically proved endometriosis. Nine of 153 (5.8%) female sibs (over age 18) of patients with histologically proved endometriosis were considered similarly affected; 10 of 123 mothers (8.1%) were affected; 19 of 276 (6.9%) of all first-degree relatives were affected. By contrast, only one of 104 (1.0%) female sibs of their husbands and only one of 107 (0.9%) mothers of their husbands were affected, significantly (p less than 0.05) less for both sibs and mothers. Several genetic etiologies can be postulated, but polygenic/multifactorial inheritance seems most likely because of (1) the 6.9% recurrence risk for all first-degree relatives and (2) observations that the 18 patients with an affected first-degree relative were more likely to have severe endometriosis than those without an affected first-degree relative.
Adolescent↗
Heritage aspects of endometriosis. II. Clinical characteristics of familial endometriosis.
Clinical characteristics of patients with histologically confirmed pelvic endometriosis who had an affected first-degree relative (N = 18) were compared to those who had no such affected relative (N = 105). The only significant difference was that 61% of individuals in the former group had severe endometriosis, compared to only 24% in the latter group. This observation is most consistent with a polygenic/multifactorial etiology, although other genetic mechanisms cannot be excluded. Our observations carry several important practical implications. First, an apparently unaffected patient with an affected first-degree relative should be counseled that her risk of developing endometriosis is 7%. This might influence the choice of contraception, the timing of pregnancy, and the extent to which aggressive diagnostic approaches (e.g., laparoscopy and curettage) would be appropriate.
Adolescent↗
Stability of sex chromosome mosaicism.
In individuals with sex chromosome mosaicism the proportions of cell lines have been reported to change over time; however, purported changes have failed to show a consistent decrease or increase in any given cell line, normal or abnormal. We, therefore, investigated three mosaic individuals: two 45,X/46,X,i(Xq) and one 45,X/46,XX. We first initiated studies which verified that the proportion of various cell lines can be reliably (reproducibly) quantitated in lymphocytes of mosaic individuals, data which surprisingly were heretofore unavailable. Having established the ability to quantitate sex chromosome mosaicism, we initiated longitudinal studies. No significant differences in proportions of mosaic cell lines were observed in the three individuals studied over various time intervals. This stability was observed in individuals with high as well as lower proportions of 45,X cells. Further studies over longer periods and with other subjects are continuing, but our preliminary studies suggest mosaicism shows longitudinal stability, at least in adults. The practical clinical significance is that mosaicism can be reproducibly quantitated from a single lymphocyte culture, indicating that a single blood sample will generally suffice for most clinical studies.
Adolescent↗
Genes, chromosomes, and reproductive failure.
Explore the source record for details and available documents.
Abortion, Habitual↗
Prenatal diagnosis of harlequin ichthyosis.
We report the successful prenatal diagnosis of ichthyosis in the fetus of a woman whose previous liveborn child was affected with "harlequin ichthyosis". The fetal diagnosis was established through analysis of ultrasonographically guided fetoscopic skin biopsies. These biopsies showed premature hyperkeratosis, most marked around hair follicles and sweat ducts, and forming plugs of hyperkeratotic debris. These observations were in distinct contrast to those in control fetuses, whose epidermis consists of squamous epithelium only a few cells in depth with minimal keratinization.
Adult↗