Heteroallelic twins and twin publications.
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Alleles↗
Biomedical subjects
H Rivera
Publications and source records attributed to H Rivera.
Neocentromere at 13q32 in one of two stable markers derived from a 13q21 break.
A 10-month-old girl with psychomotor retardation, microcephaly, bilateral microphthalmia, and postaxial polydactyly of the feet was karyotyped using banding techniques and (single or dual color) fluorescent in situ hybridization (FISH) with four probes: D13Z1/D21Z1, pancentromeric, pantelomeric, and a mix of 13q subtelomeric and 13/21 alphoid repeats. She was found to have a 47-chromosome karyotype in which a normal 13 was replaced by two stable markers derived from a breakpoint at 13q21.1, namely a del(13)(q21.1) and an isofragment(13) (qter-->q21.1::q21.1-->qter). The latter had a single C-negative but Cd-positive primary constriction at 13q32 which, however, was not obvious in about 12% of the cells. FISH studies showed that the small 13q- had the 13-centromere and a 13q telomere (as shown for a specific 13q subtelomeric signal) onto the broken end whereas the isofragment lacked alphoid signals but had 13q subtelomeric sequences on both ends. Parental karyotypes were normal. The patient's rearrangement represents the eighth chromosome-13-derived marker with a nonalphoid neocentromere located at 13q. All in all, such neocentromeres have been described in 29 markers derived from chromosomes 2, 3, 8-11, 13-15, 20, and Y, and plausibly result from the epigenetic activation of a latent centromere, which may even be a telomere with neocentric activity. The 13q telomere found in the del(13q) was probably captured from the homologous chromosome.
Abnormalities, Multiple↗
Centromere-telomere (12;8p) fusion, telomeric 12q translocation, and i(12p) trisomy.
The concurrence of a short arm isochromosome and a translocation of the entire long arm of the same chromosome to a telomere of another chromosome, implying trisomy for 4p, 5p, 7p, 9p, 10p or 12p, has been described in 13 patients. We have now used fluorescence in situ hybrization (FISH) to better characterize one of these rearrangements in which 12q was translocated to 8pter, whereas 12p was converted into an isochromosome. An alphoid centromere-12 repeat gave a strong signal on the i( 2p) and a weak but distinct signal at the breakpoint junction of the der(8), whereas the pantelomeric probe revealed three clear hybridization sites on the der(8): one at each end and another at the breakpoint junction. These findings suggest that the prime event was a post-fertilization centric fission of chromosome 12 leading to the 12q translocation via a real centromere telomere fusion and the i(12p). Alternatively, the crucial event may have been a centromere telomere recombination. An interstitial telomere has been documented by means of FISH at the breakpoint junction of the sole derivative usually present in 20 constitutional translocations including eight with a jumping behavior. In addition, six other telomeric translocations defined by banding methods, including another case of 12q translocation/i(12p), have also been jumping ones. These telomeric translocations have been de noro events and their proneness to exhibit a jumping behavior appears to be independent of the involved chromosomes, size of the translocated segments, and concomitant abnormalities.
Centromere↗
An extra idic(21)(q22.1) in a child with some features of Down's syndrome.
A 30-month-old boy with mental retardation, hypotonia, joint hyperlaxity, Brushfield spots, open mouth, distal axial triradius t", and ulnar loops on both forefingers was found to have a 47,XY, + psu idic(21)(q22.1).ish psu idic(21)(q22.1)(D13Z1/D21Z1 + + ,ETS2-) karyotype. The patient's phenotype, with only some Down's syndrome (DS) features, is probably related to his disomy for most or all of the critical region 21q22.2 q22.3 and agrees with the current notion that certain DS features may also result from 21q proximal duplications. The phenotypical comparison with 2 other patients with a similar extra idic(21) reveals some discrepancies, which may be related to the inherent clinical variability of similar imbalances: yet, a real difference between the tetrasomic segments cannot be excluded. Noticeably, all 3 patients with 21q proximal tetrasomy did not have cardiac defect and exhibited none or just one out of the five other DS phenotypic features attributed to a single gene or cluster on distal 21q22.
Adult↗
FISH and molecular study of autosomal supernumerary marker chromosomes excluding those derived from chromosomes 15 and 22: I. Results of 26 new cases.
The chromosomal origins and in some cases the molecular composition of 26 autosomal supernumerary marker chromosomes (SMC) were identified using combined fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) techniques. Fifteen were de novo, 4 maternally and 2 paternally transmitted and in 5 cases the parental origin is not known. Eleven cases were non-mosaic and fifteen cases had SMC cell lines ranging from 8-87%. Ten cases were ascertained prenatally, nine postnatally with abnormal phenotypes, three with poor reproductive histories and four co-incidentally. Five SMC were small rings from chromosomes 3, 6 (2 cases), 20 and 21; 8 were bisatellited from chromosomes 13/21 (4 cases), 14 (3 cases) and 14/22 (1 case). The remaining 13 appeared to be minutes comprising centromeric material only from chromosomes 1, 4, 12, 13/21 (2 cases), 14 (3 cases), 16 (2 cases), 19; 5/19, and a centric fusion involving 13 or 21 and 14. Euchromatin was detected in 9 out of 18 SMC tested with paints and/or PCR, and abnormal phenotypes were most commonly observed in patients with small ring shaped SMCs containing euchromatic sequences. Uniparental paternal isodisomy (UPD) for chromosome 6 was detected in one patient but was the only example of UPD for the normal homologues in association with an autosomal SMC in an overall total of 30 cases examined.
Chromosome Aberrations↗
Expression of low-density lipoprotein receptors in peripheral blood and tonsil B lymphocytes.
B lymphocytes, purified from peripheral leucocytes from young normolipaemic humans, expressed and internalized low-density lipoprotein receptors (LDLR). The expression was assessed by a monoclonal anti-LDLR. The internalization of LDL was assessed by LDL labelled with 125I (125I-LDL) and 1,1'-dioctadecyl-3,3,3',3' tetramethyl-indocarboxycyanine perchlorate (LDL-DiI). The expression of LDLR, assessed by anti-LDLR, was: 38 +/- 8% (n = 5) for fresh purified cells, 60 +/- 10% (n = 12) for non-stimulated cells, 79 +/- 5% (n = 10) for IL-2 (100 U/ml)-stimulated cells and 95 +/- 5% (n = 8) for pokeweed mitogen (PWM) (1:200 dilution)-stimulated cells. The optimal concentrations of agonist were 100 U/ml of IL-2, and 1:200 dilution of PWM. IL-2 and PWM increased the internalization of LDL-DiI by 1.5-fold. The internalization of LDL-DiI was maximal at 60 microg of protein/ml (48 +/- 8%). Scatchard analysis revealed a Kd of 3.2 +/- 0.22 x 10(-8) M and 2180 +/- 190 binding sites in non-stimulated cells, a Kd of 7.73 +/- 0.36 x 10(-9) M and 12,500 +/- 430 binding sites for IL-2 (100 U/ml)-stimulated cells, and a Kd of 7.2 +/- 0.43 x 10(-9) M and 13,250 +/- 450 binding sites for PWM (1:200 dilution)-stimulated cells. Lineweaver-Burk analysis of LDL binding (LDL-DiI) revealed that the apparent Kd for non-stimulated cells was 1.3 +/- 0.11 x 10(-8) M, and 9.2 +/- 0.2 x 10(-9) M and 7.5 +/- 0.25 x 10(-9) M for IL-2- and PWM-stimulated cells, respectively. B lymphocytes from tonsils also showed a high expression of LDLR assessed with anti-LDLR (70 +/- 6%). The high expression of LDLR and the avid internalization of LDL suggest that LDL may be important for B cell physiological responses.
Adult↗
Characterization of local memory cells in stage-classified pulmonary tuberculosis: preliminary observations.
Immunophenotype analysis and proliferative responses were investigated in bronchoalveolar lavage (BAL) cells from 21 patients with stage-classified tuberculosis: six with localized pulmonary infiltrate (LPI); seven with diffuse pulmonary infiltrate (DPI); and eight with pleural effusions (PE). Bronchoalveolar lavage cells from these patients contained a high number of cells/ml. The macrophage number was significantly lower in the DPI group (P < 0.05) compared to the LPI or PE groups. Conversely, neutrophils were markedly increased in DPI patients compared to LPI (P < 0.01) and PE (P < 0.01) patients. Lymphocyte infiltration (97.7 +/- 2.3% CD3+, > 83% alphabeta+ and CD4+ > CD8+) was observed in the three groups. A significant increase in the number of total lymphocytes (P < 0.01) and CD4+ cells (P < 0.05) was observed in the LPI group compared to the PE group. In the LPI group CD4+CD45RO+ cell infiltration was higher than CD4+CD45RA+ cells (P < 0.001), contrasting to similar numbers of these subpopulations in the DPI group. Lymphocytes from three out of three LPI patients (alphabeta+CD4+CD45RO+) responded against tuberculin purified protein derivative contrasting to the unresponsiveness of five patients with either DPI or PE. This impaired response was reverted in two out of five patients by using peripheral blood monocytes instead of alveolar macrophages. It is suggested that, in humans, alphabetaCD4+CD45RO cells are the main lymphocyte type involved in the initial local cell-mediated immune response against Mycobacterium tuberculosis.
Adolescent↗
Intrachromosomal triplication of distal 7p.
A female infant who died at 2 years of age with growth and psychomotor retardation, wide anterior fontanelle, downward slanting palpebral fissures, large, simple ears, joint dislocation/contractures, recurrent infections, and severe pulmonary hypertension was found to have a de novo 7p+ chromosome. The G banding pattern was suggestive of a triplication of 7p21.3 and 7p22; results of fluorescence in situ hybridisation studies using a chromosome 7 specific library, a subtelomeric 7p repeat (109A6), and yeast artificial chromosome clones 786g1 and 850a1, which are respectively associated with the (CA)n repeat markers D7S517 and D7S513, supported the cytogenetic interpretation and showed that the middle repeat was inverted. The patient's phenotype was consistent with the 7p duplication syndrome, allowing for the effects of the extra burden introduced by the partial tetrasomy. The present rearrangement may have resulted from several meiotic events occurring at the four chromatid stage, namely an unequal crossover or interhomologue translocation with points of exchange at 7p22 and 7p15 followed by the inverted insertion of 7p21.3-->p21.2 at the former breakpoint junction; moreover, a further duplication including D7S517 within the terminal 7p22 band is also required.
Abnormalities, Multiple↗
Modulation of estrogen receptor levels in mouse uterus by protein kinase C isoenzymes.
We have recently shown that protein kinase C (PKC) modifies estrogen receptor (ER) binding and modulates the responsiveness to estrogens in a clonal osteoblast-like cell line stably transfected with the ER. The purpose of the present study was to determine whether the interaction observed between the ER and PKC signaling in these cells occurs in additional estrogen target organs, such as the uterus. When uteri were incubated for 2 h with increasing concentrations of a kinase inhibitor (H7), ER binding was enhanced in a dose-dependent manner. Stimulation of PKC with phorbol ester reduced PKC activity levels, but increased ER binding. Interestingly, the changes in binding appeared to be due primarily to alterations in cytosolic ER levels, as binding in the nuclear fraction was minimally enhanced. When levels of ER messenger RNA were evaluated by Northern blot analysis, no differences were observed among the H7- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated and untreated groups. Western blot analysis, however, demonstrated that levels of ER cytosolic protein in the H7-, TPA-, and staurosporine-treated groups were increased relative to those in the untreated controls. When uteri were incubated with diethylstilbestrol in the presence of either H7 or TPA, no change in cytosolic ER levels was found, suggesting that only unoccupied ERs are responsive to modulation by PKC. Western blotting of the various PKC isoforms indicated that although PKC alpha, -beta1, -betaII, -delta, and -zeta are expressed in the uterus, only PKC alpha and -beta1 are translocated from the soluble to the particulate fraction and then degraded after phorbol ester stimulation. Hence, one or both of these latter PKC isoforms may regulate cytosolic ER levels. Collectively, these data indicate that PKC may play an important role in the modulation of uterine ER levels and that PKC may exert its effect on the ER at some posttranscriptional or posttranslational step. Finally, our results show that an ER-PKC interaction occurs in a whole organ such as the uterus and that this interaction may be important in the regulation of the ER activity in a variety of estrogen-responsive tissues.
Animals↗
Brachydactyly and fragile site at 16q22: a chance association.
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Adult↗
A conservative surgical approach of osteochondroma affecting the mandibular condyle.
An osteochondroma of the condyle in a 49-year-old venezuelan female patients is reported. Clinical, radiological and histopathological features of the tumor are described. A wide local surgical excision permitted the patient to regain normal function.
Female↗
Publication and accountability of case reports.
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Journalism, Medical↗
Impairment of natural killer (NK) cytotoxic activity in hepatitis C virus (HCV) infection.
In the present study, we evaluated the NK cell cytotoxic activity in a group of HCV-infected individuals. Although the number of NK cells present in the peripheral blood of the HCV-infected patients was comparable to non-infected individuals, spontaneous NK cytotoxicity was four-fold lower (P < 0.001) than in normal donors. This functional impairment was not overcome by depletion of adherent or B cells, and it was partially restored by short-term (18 h) stimulation with IL-2. However, long-term stimulation (72 h) with this lymphokine induced activated killer cell (LAK) activity comparable to normal controls. The reduction in NK cytotoxic response does not seem to be due to soluble suppressive factors, since incubation of normal peripheral blood mononuclear cells (PBMC) with infectious HCV serums for a 4-h period does not affect NK spontaneous cytotoxic activity. Successful in vitro infection of PBMC with HCV infectious serum also resulted in an impairment of NK cytotoxicity, suggesting that altered NK function is associated with HCV infection and may be responsible, at least in part, for the chronicity of the infection.
Adult↗
Low density lipoprotein receptor expression and function in human polymorphonuclear leucocytes.
Low density lipoprotein receptors (LDLR), capable of internalizing LDL, are expressed in polymorphonuclear neutrophils (PMN). The expression was assessed using anti-LDLR antibody by flow cytometry. The internalization of LDL was assessed by: (i) quantification of the uptake of labelled LDL with 1,1'-dioctadecyl-3,3,3',3' tetramethyl-indocarboxycyanine perchlorate (DiI) by flow cytometry; and (ii) the binding of LDL-125I. In fresh purified cells, Lineweaver Burk analysis of LDL binding (LDL-DiI) revealed that the calculated Kd (internalized LDL) for PMN (15.0 x 10(-9) M) is lower than the Kd for monocytes (1.1 x 10(-7) M) and the Kd for lymphocytes (3.2 x 10(-7) M). Scatchard analysis (LDL-125I) revealed 25,000 binding sites and a Kd of 9.6 x 10(-9) M for PMN. The interaction of LDL with its receptor caused a two-fold fast (peak at 1 min) and transient increase in the oxidative burst, measured by the formation of 2',7' dicholoflurescein (DCF) by flow cytometry. This effect was not observed in monocytes or lymphocytes, and it was blocked by anti-LDLR antibody. The stimulation of LDL was optimal at 10 microg of protein/ml. LDL was able to suppress DCF formation induced by phorbol myristate acetate (PMA) and PMA was unable to further stimulate LDL-treated cells, suggesting protein kinase-C (PKC) involvement in LDL effects. Using a PKC assay, LDL was shown to induce a two-fold increase in PKC translocation to the membrane. Thus, LDL increases PMN oxidative burst through a PKC-dependent pathway.
Humans↗
Familial inv(X) (p22q22): ovarian dysgenesis in two sisters with del Xq and fertility in one male carrier.
A recombinant chromosome with Xp duplication and Xq deletion was found in two sisters with normal height and gonadal dysgenesis. Their mother and other four relatives, including a fertile male, carried an inv(X) (p22q22); the inverted X was randomly inactivated in one female carrier. The abnormal X chromosome showed inactivation in all the examined cells. This is the tenth report of a recombinant X chromosome. A review of the literature shows that: i) most female carriers of inv(X) are phenotypically normal and fertile; ii) recombinants having short-arm duplication and long-arm deletion are associated with ovarian failure and normal or tall stature, whereas the reciprocal recombinants are compatible with fertility but cause short stature; and iii) except for one index case, all male carriers have a normal phenotype and 11 of them (from eight families) are of proven fertility. Moreover, no instance of male infertility has been documented.
Adult↗
Functional Xp disomy and de novo t(X;13)(q10;q10) in a girl with hypomelanosis of Ito.
We report on a 16 month old girl with hypomelanosis of Ito and a balanced de novo (X;13)(q10;q10) translocation in which the der(Xp13q) had the X centromere (as assessed by FISH with the DXZ3 probe). A functional Xp disomy was shown in a small proportion of cultured lymphocytes by means of a BrdU terminal pulse. This observation supports the notion of a distinct form of hypomelanosis of Ito resulting from a functional Xp disomy.
Adult↗
C-anaphases (common variant) are unrelated to colchicine and phytohemagglutinin.
We evaluated the effect of different concentrations of colchicine (0.0, 0.1, 0.3, 0.5 microgram/ml) and phytohemagglutinin (PHA) (0.10, 0.15, 0.20 microgram/ml) on the rate of C-anaphases in lymphocyte cultures from five healthy individuals with the common variant of C-anaphases. For each of the 12 possible combinations, two subjects were randomly tested. The frequency of these variant figures was < 3%; a single-culture (out of six with the colchicine concentration of 0.1 microgram/ml) lacked C-anaphases. Multiple variance and Student's t tests revealed, as the only significant difference, a decrease with the colchicine concentration of 0.3 microgram/ml compared with the cultures without colchicine (p < 0.05), which exhibited the greatest ratio of C-anaphases. The PHA had no influence on the frequency of C-anaphases. We conclude that the common variant of C-anaphases is unrelated to the colchicine and PHA concentrations tested; moreover, our data confirm the occurrence of such a mitotic variant in colchicine-free cultures.
Adult↗
A further whole arm 1;19 translocation with alpha-satellite DNA breakage.
A balanced whole arm translocation (1;19)(p10;q10) was found in a woman with normal phenotype ascertained through a fragile X survey. Chromosome painting with the specific libraries confirmed the cytogenetic diagnosis. Fluorescence in situ hybridization with a chromosome-1 alpha-satellite probe revealed that the breakpoint in chromosome 1 split the alpha-satellite sequences into two blocks. The review of constitutional whole arm translocations revealed a greater participation of some chromosomes with recurrence of translocations t(1;19)(1p19q;1q19p), t(18;20)(18p20q;18q20p) and t(X;17)(Xp17q;Xq17p). The alpha-satellite breakage documented in some derivatives of the recurrent translocations may be related to highly homologous subsets in the involved chromosome pairs, which belong to alpha-satellite subfamilies 1, 2 and 3 respectively. Probably this leads to abnormal chromosome pairing and thus to whole arm translocations.
DNA, Satellite↗