American journal of medical genetics. Supplement最新文献

{"title":"Trisomy 21 (Down Syndrome).","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"1-325"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13303643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunology of Down syndrome: a review.","authors":"A G Ugazio,&nbsp;R Maccario,&nbsp;L D Notarangelo,&nbsp;G R Burgio","doi":"10.1002/ajmg.1320370742","DOIUrl":"https://doi.org/10.1002/ajmg.1320370742","url":null,"abstract":"<p><p>Subjects with Down syndrome (DS) have a high mortality due to infections and a high risk of developing malignancies. These observations, together with the demonstration of a frequent occurrence of HBsAg carrier state and of autoantibodies, have prompted investigations of the immune function in DS. Thymic morphological and functional abnormalities have been demonstrated. Peripheral blood mononuclear cells of DS subjects have been shown to include a high number of T lymphocytes with low avidity for sheep erythrocytes and a very high percentage of cells with an NK phenotype. However, NK activity is low in DS. Production of some important cytokines, such as IL-2, is depressed, thus contributing to T-cell derangement. Abnormalities of the B-cell compartment were also demonstrated, with a tendency towards high IgG and low IgM serum levels. Controversial results have been obtained with regard to antigen-specific antibody response. Also phagocytes of DS subjects display some characteristic functional impairments, with low chemotactic ability and reduced production of oxygen radicals. Despite the clearly established and rather detailed evidence of immune derangements, therapeutic trials have been anecdotal and resulted in marginal effects. HBV vaccination is highly advisable in DS because of the high risk of becoming chronic HBV carriers once infected.</p>","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"204-12"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.1320370742","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13304138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humoral immunodeficiencies in Down syndrome: serum IgG subclass and antibody response to hepatitis B vaccine.","authors":"M A Avanzini,&nbsp;V Monafo,&nbsp;M De Amici,&nbsp;R Maccario,&nbsp;G R Burgio,&nbsp;A Plebani,&nbsp;A G Ugazio,&nbsp;L A Hanson","doi":"10.1002/ajmg.1320370746","DOIUrl":"https://doi.org/10.1002/ajmg.1320370746","url":null,"abstract":"","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"231-3"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.1320370746","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13304142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosome fragile sites in Down syndrome patients.","authors":"B Tedeschi,&nbsp;P Vernole,&nbsp;D Caporossi,&nbsp;B Nicoletti","doi":"10.1002/ajmg.1320370739","DOIUrl":"https://doi.org/10.1002/ajmg.1320370739","url":null,"abstract":"<p><p>We report on the fragile site expression in lymphocytes from 16 Down syndrome (DS) men aged 24 to 52 years. Among rare fragile sites, 16q22 has been reported to be induced or enhanced by alpha-interferon. Since DS cells have three copies of the receptor for alpha-interferon, we hypothesized a possible enhancement of 16q22 expression. This fragile site has also been related to a specific rearrangement in M4 acute nonlymphocytic leukemia. In view of the high incidence of acute leukemia in DS subjects, we studied the expression of 16q22 in lymphocyte cultures treated with 5-bromodeoxyuridine or alpha-interferon. We also studied whether the repair deficiency of DS cells could affect the expression of aphidicolin-induced fragile sites. The level of chromosomal aberrations was compared with that found in aphidicolin-treated cultures from 12 normal subjects of the same age. We found neither spontaneous or BrdU-induced fragility at 16q22 nor induction by alpha-interferon. Chromosomal breakage rate was increased in alpha-interferon-treated cultures in comparison with control cultures of the same subjects. Aphidicolin-induced fragile sites expression in DS patients did not differ significantly from that found in the lymphocyte cultures from control subjects.</p>","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"192-4"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.1320370739","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13303555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrathymic deficient expansion of T cell precursors in Down syndrome.","authors":"P Musiani,&nbsp;S Valitutti,&nbsp;F Castellino,&nbsp;L M Larocca,&nbsp;N Maggiano,&nbsp;M Piantelli","doi":"10.1002/ajmg.1320370744","DOIUrl":"https://doi.org/10.1002/ajmg.1320370744","url":null,"abstract":"<p><p>To correlate the intrinsic cellular immunodeficiency, which is a major cause of increased susceptibility to polytopic infections in Down syndrome (DS) patients, with the histologic abnormalities observed in the thymus of these patients, we have studied thymus fragments and thymocyte cell suspensions from 15 non-institutionalized DS subjects. Comparing to the control age-matched samples, a reduced thymic cortex and a distinct depletion of CD1-positive (+) cells was observed by immuno-histologic examination. The phenotypic analysis of unselected thymocytes showed a significant reduction of CD3+, CD1+, CD4+, and CD8+ cells. When the total thymocyte population was separated into 10 fractions, using a continuous Percoll density gradient, a difference in cell distribution was observed. DS thymuses are almost devoid of high-density thymocytes (fractions 6-9) while more than 75% of the cells were recovered in the lightest 3 fractions (Frs). In addition, these thymuses were characterized by a marked depletion of CD1+ cells and by a conspicuous reduction of CD3+ cells normally present in the high-density Frs. On the other hand, the lightest 3 Frs of DS subjects were enriched in low-density CD1+ cells. Although enriched in these cells, normally characterized by a high mitotic activity, Fr1 DS thymocytes showed a reduced spontaneous proliferative capacity. When the expression of T cell receptor alpha- and beta-subunits was studied, the percentages of cells stained with anti-alpha and anti-beta antisera were found to be reduced in DS unfractionated thymocytes. The reduced number of high-density CD1+ thymocytes associated with a reduced spontaneous proliferative activity of low-density CD1+ thymocytes suggests that in DS thymuses there is a deficient expansion of immature T cells, resulting in a reduction of the various thymocyte subpopulations, including the thymocyte pool which differentiates into functionally mature T cells expressing the alpha-beta T cell receptor.</p>","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"219-24"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.1320370744","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13304140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased level of T cell receptor expression by Down syndrome (trisomy 21) thymocytes.","authors":"M Murphy,&nbsp;M J Lempert,&nbsp;L B Epstein","doi":"10.1002/ajmg.1320370747","DOIUrl":"https://doi.org/10.1002/ajmg.1320370747","url":null,"abstract":"<p><p>Individuals with Down syndrome (DS) have an enhanced susceptibility to viral and bacterial infections. Previous studies by our laboratory demonstrated alterations in the proportions of peripheral T cell subpopulations and decreased proliferative, interleukin-2, and antibody responses to viral and bacterial antigens in DS. These data suggested that DS lymphocytes have a diminished ability to recognize and respond to specific antigen. It has been proposed that the abnormalities in T cell function in DS may be a result of aberrant T cell maturation within the DS thymus. Therefore, we examined by immunofluorescence and flow cytometry the cell surface expression of the alpha,beta chains of the T cell receptor (TCR alpha,beta) and the associated CD3 molecule on thymocytes from 10 DS and 27 control children. A significantly smaller proportion of cells expressing high levels of TCR alpha,beta was observed in DS thymuses compared to controls (17.0% vs. 34.3%, respectively; P less than 0.01). A similar observation was made for CD3, a molecule responsible for signal transduction through the TCR, where a lower proportion of cells expressing high levels of CD3 was found in DS compared to controls (18.4% vs. 43.3%, respectively; P less than 0.001). These data are evidence for aberrant T cell maturation in DS. In addition, our findings of decreased acquisition of high levels of the molecules which are critical for antigen-specific recognition by T cells suggest a possible mechanism for the decreased T cell function found in individuals with DS.</p>","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"234-7"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.1320370747","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13304143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down syndrome children often have brain with maturation delay, retardation of growth, and cortical dysgenesis.","authors":"K E Wisniewski","doi":"10.1002/ajmg.1320370755","DOIUrl":"https://doi.org/10.1002/ajmg.1320370755","url":null,"abstract":"<p><p>All Down syndrome (DS) children have different degrees of developmental disabilities, developmental delay, and developmental brain abnormalities associated with CNS maturation delay and cortical dysgenesis. We have examined 780 occipitofrontal circumferences (OFC), mean and +/- SD, of DS children from birth to age 5 years. Also, gross and microscopic neuropathological studies in the same age group were performed, with special attention to brain weight (BW), shape, myelin formation, cortical organization of 101 DS and 80 non-DS individuals; ultrastructural studies were also performed on selective cases (five DS and five non-DS). The OFC was plotted on Nellhause curves and showed microcranium after mid-infancy in most cases. Twenty percent of DS children had an OFC in the lower normal range. The brain shape in DS newborn infants was the same as in non-DS infants, but after 3-5 months of age in DS infants the antero-posterior diameter was found to be shorter than in non-DS infants. Narrowness of the superior temporal gyrus was noted in 34 of 101 (33%) of DS brains. Microscopic examination showed myelination delay in 22.5% DS and only in 6.8% non-DS children. Morphometric studies in DS cases from birth showed fewer neurons (20-50% less), lower neuronal densities, and neuronal distribution, especially of cortical layers II and IV. Ultrastructurally in DS, the synaptic density, synaptic length, and contact zones were found to be abnormal. The retardation of brain growth, maturation delay, and cortical dysgenesis present in DS children most likely are regulated by the extra chromosome 21, but the gene responsible for the abnormalities remains to be determined.</p>","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"274-81"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.1320370755","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13304729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nondisjunction of chromosome 21.","authors":"N Takaesu,&nbsp;P A Jacobs,&nbsp;A Cockwell,&nbsp;R D Blackston,&nbsp;S Freeman,&nbsp;J Nuccio,&nbsp;D M Kurnit,&nbsp;I Uchida,&nbsp;V Freeman,&nbsp;T Hassold","doi":"10.1002/ajmg.1320370735","DOIUrl":"https://doi.org/10.1002/ajmg.1320370735","url":null,"abstract":"<p><p>Chromosome heteromorphisms and restriction fragment length polymorphisms were used to study the origin of the extra chromosome in 54 trisomy 21 conceptuses. The parental origin was determined in 43 cases, with 39 (91%) being maternally and 4 (9%) parentally derived. Analysis of recombination demonstrated the presence of one or two cross-overs in most cases for which sufficient information was available, suggesting that failure to pair/exchange at meiosis I is relatively unimportant in the genesis of trisomy 21.</p>","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"175-81"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.1320370735","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13140285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoradiographic studies of neurotransmitter receptors in the brain of newborn infants with Down syndrome.","authors":"J Flórez,&nbsp;C del Arco,&nbsp;A González,&nbsp;J Pascual,&nbsp;A Pazos","doi":"10.1002/ajmg.1320370759","DOIUrl":"https://doi.org/10.1002/ajmg.1320370759","url":null,"abstract":"<p><p>The autoradiographic pattern of cholinergic muscarinic receptors in the brain of two newborn infants with Down syndrome (DS) (stillbirths, 31 and 39 gestational weeks), were compared with that of age-matched control fetuses. Densities and distribution patterns of muscarinic receptors in the forebrain were similar in both groups. However, a marked receptor reduction was found in the midbrain (superior colliculus, substantia nigra) of DS brains compared to control brains. The results indicate the existence of deficient prenatal development of cholinergic transmission in DS that may be responsible for the occurrence of specific difficulties in early postnatal life.</p>","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"301-5"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.1320370759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13304680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Derangement of non-specific immunity in Down syndrome subjects: low leukocyte chemiluminescence activity after phagocytic activation.","authors":"F Licastro,&nbsp;C Melotti,&nbsp;R Parente,&nbsp;L J Davis,&nbsp;M Chiricolo,&nbsp;M Zannotti,&nbsp;F Barboni","doi":"10.1002/ajmg.1320370749","DOIUrl":"https://doi.org/10.1002/ajmg.1320370749","url":null,"abstract":"<p><p>Metabolic activation of peripheral blood leukocytes (chemiluminescence) from 27 children with Down syndrome (DS) and 23 age and sex-matched control children after phagocytic stimulation by opsonized zymosan particles was investigated through a chemiluminescence assay. Using autologous plasma or serum as opsonizing media, phagocytic activity of circulating leukocytes was significantly decreased in DS subjects. A further decrease of phagocytic activity was found in neutrophils from DS children, when normal heterologous plasma or sera were used. On the other hand, sera or plasma from DS subjects significantly increased phagocytic activation of leukocytes from normal donors. In DS subjects opsonizing agents such as serum immunoglobulins and complement fractions were in the normal ranges of concentration. Thus, the impaired chemiluminescence of neutrophils was mainly due to a metabolic impairment at the cellular level. A decreased production of radicals derived from the oxygen metabolism in neutrophils may be an important step of immune derangement leading to the increased incidence of infectious diseases frequently associated with DS.</p>","PeriodicalId":77486,"journal":{"name":"American journal of medical genetics. Supplement","volume":"7 ","pages":"242-6"},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.1320370749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13304724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}