Rett syndrome and fragile site in Xp22.
Explore the source record for details and available documents.
Autistic Disorder↗
Biomedical subjects
M Rocchi
Publications and source records attributed to M Rocchi.
The human genes for hemophilia A and hemophilia B flank the X chromosome fragile site at Xq27.3.
Two DNA recombinant clones, shown by separate studies to contain DNA sequences homologous to the genes coding for the human blood coagulation Factors VIII and IX, were hybridized in situ to metaphases or prometaphases derived from patients with the fragile-X syndrome and from a normal control. The results of these experiments indicate that (i) both genes are located in the subtelomeric region of the long arm of the human X chromosome flanking the fragile site at Xq27.3, (ii) the resolution of this localization is approximately 0.5% the length of the human haploid genome, i.e., 1.8 X 10(7) bp, (iii) the linear order of loci within the above region is Factor IX-fragile site-Factor VIII-Xqter. Both the localization and the linear order of these loci have been confirmed by Southern blotting studies using the same molecular probes and a panel of rodent-human somatic cell hybrids known to have retained different segments of the human X chromosome. The findings described herein and the knowledge that Factor IX deficiency recombines freely with at least two loci of the G6PD cluster support our hypothesis that the chromosomal region which includes the fragile-X site is normally a region of high meiotic recombination.
Chromosome Mapping↗
Cytologic demonstration of differential activity of rRNA gene clusters in different human tissues.
rRNA gene activity was evaluated by cytologic methods in cultured human cells from two different tissues grown under controlled experimental conditions. The modal and average numbers of silver positive nucleolus organizers (NOs) per cell as well as the distribution of cells with different numbers of silver positive NOs and different combinations of D- plus G-group silver stained chromosomes, were evaluated. Statistically significant differences in the average number of silver positive NOs per cell between leukocytes and fibroblasts grown under standard experimental conditions have been demonstrated. The observed differences became sharper in cells cultured under more restrictive conditions. Also, differences in the frequency of silver positivity of specific chromosomal NOs located on individually identified chromosomes were observed in cells from the same tissue. Furthermore, differences in the frequency of activation of rDNA clusters located on the same chromosome were also observed between cells from the two tissues. The possible biologic meanings of these findings are discussed.
Cells, Cultured↗
Hormone-modulated rRNA gene activity is visualized by selective staining of the NOs.
The role of Growth Hormone and Dexamethasone in the regulation of rRNA gene activity was evaluated on cultured human fibroblasts by the cyto-chemical method of selective silver staining. By this method the transcriptionally active r-gene clusters can be specifically visualized in individual cells. Statistically significant increases in the rate of rRNA transcriptional activity were demonstrated after hormone administration.
Adult↗
The transcriptional activity of individual ribosomal DNA gene clusters is modulated by serum concentration.
The activity of ribosomal gene clusters has been studied by cytological methods in human cultured cells grown in different amounts of serum under controlled experimental conditions. It has been shown that increasing amounts of serum induce an increase in ribosomal RNA synthesis at the single cell level. Furthermore, the concomitant identification of individual rRNA gene clusters by fluorescent techniques allowed us to demonstrate: (1) that individual gene clusters have differential transcriptional activity and differential frequency of activation; (2) that ribosomal gene activity is closely associated with the amount of silver-positive gene product and; (3) that environmental variations modulate rRNA synthesis by repressing or derepressing specific gene clusters.
Blood↗
A two step model for mammalian X-chromosome inactivation.
Explore the source record for details and available documents.
Animals↗
Mapping of X-linked Becker muscular dystrophy through crossovers identified by DNA polymorphisms and by haplotype characterization in somatic cell hybrids.
The analysis of 10 X-linked DNA polymorphisms (five mapping on the short arm and five on the long arm) in two Becker muscular dystrophy pedigrees has been used to localize this gene in the known sequence of DNA polymorphic markers on the X chromosome. In the first pedigree, the carrier mother, whose phase for Becker and for five informative polymorphisms is known, has transmitted a double recombinant X chromosome to one of her two affected sons. The discordance between these two affected brothers for four of the five informative polymorphisms indicates that the Becker gene is located between RC8 or D2 on one side and pDP34 on the other. In the second pedigree, where the maternal grandfather is dead and two maternal first cousins are affected, the phase of DNA polymorphic alleles has been identified in somatic cell hybrids resulting from the fusion of hamster fibroblasts with lymphocytes of the mothers and aunt of the patients. The discordance between the two first cousins for two of the four informative DNA polymorphisms is best explained by the occurrence of a single recombination in the X chromosome carried by one of them. This result further restricts the localization of the Becker gene to a region of the short arm delimited by B24 and L 1.28. Regional and fine gene mapping through the approach described in this paper should become useful in the future for X-linked as well as for autosomal genes.
Animals↗
Genes controlling gp25/30 cell-surface molecules map to chromosomes X and Y and escape X-inactivation.
The monoclonal antibody AbO13 defines a cell-surface antigen that is expressed on most cultured human cells, but not on rodent cells. AbO13 precipitates glycoproteins of 25,000 and 30,000 mol. wt. from lysates of [3H]glucosamine-labeled human cells. Results of the serological typing of a panel of 25 rodent-human somatic cell hybrid clones show that reactivity with AbO13 segregates with the human X and Y chromosomes. The presence of either of these chromosomes is sufficient for O13 expression on the hybrid cell surface. Analysis of hybrid clones containing human X chromosomes with karyotypically defined deletions permitted the regional assignment of the X-linked gene locus controlling the expression of O13 to Xp22-pter. In addition, AbO13 is reactive with Chinese hamster-human hybrids derived from fibroblasts of a 49,XXXXX individual that contained only inactivated copies of the human X chromosome. These results suggest that the X-linked locus determining the expression of O13 is not subject to X-inactivation.
ABO Blood-Group System↗
A prenatally detected inv dup(15).
An extra G group-like chromosome was found in an amniotic fluid cell culture. With multiple banding techniques it was identified as inv dup(15). BUdR incorporation was used to determine the lateral asymmetry of the marker, which consisted of 2 distal spots arranged contralaterally, consistent with DNA polarity conservation in chromosome rearrangements.
Adult↗
Cytological mapping of the human glucose-6-phosphate dehydrogenase gene distal to the fragile-X site suggests a high rate of meiotic recombination across this site.
The human gene for glucose-6-phosphate dehydrogenase (G6PD) has been subregionally mapped to band Xq28 by segregation analysis in rodent-human somatic cell hybrids [Pai, G. S., Sprinkel, J. A., Do, T. T., Mareni, C. E. & Migeon, B. R. (1980) Proc. Natl. Acad. Sci. USA 77, 2810-2813]. We have previously reported a common type of X-linked mental retardation associated with an inducible fragile site at Xq27-Xq28 segregates in a close linkage relationship with a G6PD variant, but the relative position of G6PD with respect to the fragile site has not yet been established. This fragile-X syndrome has been shown to be closely linked also to a Taq I restriction fragment length polymorphism detected by a cDNA probe for factor IX, and the latter locus has been mapped to the subtelomeric region Xq26-Xq28 [Camerino, G., Mattei, M. G., Mattei, G. F., Jaye, B. & Mandel, J. L. (1983) Nature (London) 306, 701-704]. The in situ hybridization studies reported here provide strong evidence that G6PD is located on the Xq telomeric fragment distal to the fragile site. These observations and the well-established knowledge that the genes for Deutan and Protan colorblindness are closely linked to G6PD, but segregate independently of factor IX deficiency, suggest that the fragile site associated with this type of X-linked mental retardation occurs in a region prone to high frequency of meiotic recombination.
Animals↗
A young girl with ring(18) mosaicism: cytogenetic studies and PEP A mapping.
A young girl with 46,XX,r(18)/46,XX/45,XX,-18 chromosome constitution is reported. She displays a slight degree of mental retardation. The line with the ring chromosome predominates in blood lymphocytes. In skin fibroblast culture the ring(18) line showed a constant decreasing trend, from 45% at the first passage, down to its disappearance at the 19th passage, where only 46,XX cells were observed. The child/mid parents' ratio of Peptidase A activity in red cells was 0.36. The Peptidase A activity in a fibroblast clone 46,XX,r(18) was 0.55 compared to the 46,XX line. These data suggest that the PEP A locus was lost in ring formation.
Adolescent↗
Treated glass coverslips for in situ culture of amniotic cells: better cell adhesion and growth than on plastic.
Explore the source record for details and available documents.
Amnion↗
Brief report: linkage between G6PD and fragile-X syndrome.
Eighteen Sardinian pedigrees segregating for the X-fragile site syndrome were studied with respect to the segregation of the fragile site (FS) at Xq28, mental retardation, and macro-orchidism. No exception was found in the association of this symptomatic triad (MOM-X) in 41 out of 42 patients examined. The exceptional individual had micro- rather than macro-orchidism and was found to have a 47, XXY sex chromosome complement. In six informative sibships, the MOM-X syndrome was found to segregate in close linkage association with G6PD-deficiency or protan colorblindness. The maximum likelihood estimate of recombination if 6% with 90% fiducial limits between 2.5 and 19.5% and an odds ratio in favor of measurable linkage of 428:1. However, no hint of measurable linkage was found in six pedigrees segregating for G6PD and the Renpenning syndrome or other unspecified types of X-linked mental retardation. These data give strong support to the generally held hypothesis that the FS at Zq28, characteristic of the MOM-X syndrome, is a direct expression of a genetic change in the same chromosomal region. They also clearly suggest that X-linked MR without FS may be the result of different allelic mutations at the same locus.
Color Vision Defects↗
X chromosome replication patterns in a case of X;9 balanced translocation.
A case of X;9 balanced translocation in a female with amenorrhoea is reported. The X breakpoint was at Xq21, inside the 'critical region'. The normal X was consistently late replicating in blood lymphocytes and skin and ovary fibroblasts.
Adult↗
[Prognostic evaluation with invasive technics in patients with hyperkinetic ventricular arrhythmias].
The prognostic value of induction of ventricular tachycardia (VT) by programmed electrical stimulation (PES) was analyzed in 123 patients: 64 (Group I) with spontaneous recurrent VT and 59 (Group II) without a history of serious arrhythmias. Thirty-three patients with spontaneous VT underwent coronary and left ventricular angiography to compare electrical instability with the presence of ventricular disfunction and/or the extent of coronary artery disease (CAD). PES reproducibly induced VT in 49/64 patients with spontaneous VT (sensitivity = 77%) and in 6/59 patients without VT (specificity = 90%). Twenty-two patients (66%) had ventricular disfunction defined by an ejection fraction of less than or equal to 40% or regional wall motion abnormalities. Only 4 patients (33%) had proximal 3-vessel CAD. The mean follow-up period was 16 +/- 12 months. Eight of Group I patients died suddenly and 24 had recurrent symptomatic VT. Three of Group I patients died (1 cardiac failure, 2 non-cardiac deaths), all the survivors were free of serious arrhythmias. In Group I patients mortality was correlated with: recent anterior myocardial infarction, inducible sustained VT with PES, ejection fraction less than or equal to 0.40, ventricular ipoasynergy and or at least one coronary stenosis greater than or equal to 70%. This study suggests that inducible VT is a marker of the risk of sudden death. Electrical instability may occur independent from the etiology of cardiopathy, ventricular disfunction and extent of CAD, but these parameters are correlated to global and sudden mortality in the group of patients with spontaneous VT.
Adult↗
Cytogenetic findings in 4952 prenatal diagnoses. An Italian collaborative study.
The development of prenatal diagnosis in Italy was made difficult by the restrictions of the old abortion law and only in recent years has a consistent number of cases been investigated. We report the experience on prenatal chromosome diagnosis of ten Italian centers participating in a collaborative study on 4952 diagnoses performed from 1972 to 1980. The main indication groups were: advanced maternal age (2882 cases), previous child with chromosome anomaly from parents with normal karyotype (847 cases), and chromosome anomaly in one parent (97 cases). The other indications for amniocentesis, including cases without a cytogenetic risk, have been assembled into a "miscellaneous" group (1126 cases). We found 125 abnormal fetal karyotypes (2.5%) of which 89 were unbalanced (1.8%). The frequencies and types of chromosome anomalies are reported in detail for each indication group and are compared with the corresponding one from the European Munich Conference. The great majority of these Italian data were not included in the Munich report.
Chromosome Aberrations↗
[Disorders of formation and conduction of the cardiac impulse in hypertrophic and congestive primary myocardiopathy].
Little information is available regarding cardiac automatism and conduction disturbances in patients affected by congestive (CCM) or hypertrophic (HCM) cardiomyopathies. For this reason 29 patients with HCM (10 cases) and CCM (19 cases) and disturbances of sinus node automaticity or AV conduction underwent an electrophysiologic study. Eight patients affected by HCM were also submitted to cardiac catheterization. Sinus node function was normal in each of the HCM patients, and impaired in 6 of the 19 CCM patients. The intra-atrial conduction was prolonged in only one CCM case. One HCM and 2 CCM patients showed an impaired intranodal AV conduction. Thirteen patients (44%) showed a prolonged HV interval (3 HCM and 10 CCM patients). No calcific deposits on the aortic valve were discovered by X ray stratigraphic examination in any of the patients. In 6 cases a progression of the conduction disturbances was observed. Ventricular pre-excitation was present in 4 patients (13%).
Adolescent↗
[Transoesophageal atrial recording and pacing. Usefulness in the diagnosis and treatment of sinus node dysfunctions and hyperkinetic arrhythmias (author's transl)].
Explore the source record for details and available documents.
Arrhythmias, Cardiac↗