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Biomedical subjects

O Zuffardi

Publications and source records attributed to O Zuffardi.

At least 91 records · Page 5Linked to original sources
PubMed1990

Nonreciprocal and jumping translocations of 15q1----qter in Prader-Willi syndrome.

We analyzed 33 cases of Prader-Willi syndrome (PWS) (including 2 personal observations) with translocations of 15q1----qter onto the terminals of different, apparently whole chromosomes. In all but one of the 23 informative cases the translocations was de novo. Thirty of the patients were unbalanced and 27 had a 45-chromosome constitution compatible with a 3:1 segregation. One balanced and 2 unbalanced translocations were jumping ones. The possible existence of actual non-reciprocal translocations in man is indicated by the following considerations about these and other PWS-associated rearrangements: 1) The observed excess of de novo translocations; 2) the relatively frequent familial occurrence of reciprocal 15q translocations; 3) the concurrence in 3 terminal translocation cases of an idic (15); 4) the visualization of jumping terminal translocations as simple transpositions rather than as successive reciprocal exchanges; 5) the predominance of true isodicentrics in PWS patients with extra inv dup(15) chromosomes; and 6) the rarity of extra derivatives resulting in 15q proximal tertiary trisomy. Additional findings in the present series were normal parental age in the de novo 45-chromosome cases, an apparently random distribution of telomeric breakpoints, and the occurrence of different breakpoints within the 15q1 region.

Adult↗
PubMed1990

Deletion of specific sequences or modification of centromeric chromatin are responsible for Y chromosome centromere inactivation.

Stable dicentric chromosomes behave as monocentrics because one of the centromeres is inactive. The cause of centromere inactivation is unknown; changes in centromere chromatin conformation and loss of centromeric DNA elements have been proposed as possible mechanisms. We studied the phenomenon of inactivation in two Y centromeres, having as a control genetically identical active Y centromeres. The two cases have the following karyotypes: 45, X/46,X,i(Y)(q12) and 46,XY/47,XY,+t(X;Y) (p22.3;p11.3). The analysis of the behavior of the active and inactive Y chromosome centromeres after Da-Dapi staining, CREST immunofluorescence, and in situ hybridization with centromeric probes leads us to conclude that, in the case of the isochromosome, a true deletion of centromeric chromatin is responsible for its stability, whereas in the second case, stability for its stability, whereas in the second case, stability of the dicentric (X;Y) is the result of centromere chromatin modification.

Adolescent↗
PubMed1990

Chromosome imbalance, normal phenotype, and imprinting.

A duplication of the sub-bands 1q42.11 and 1q42.12 was found in a boy and his mother. The proband has short stature (around the 10th centile) but a normal phenotype and psychomotor development. His mother is also asymptomatic. We found 30 published cases of normal subjects with an imbalance of autosomal euchromatic material. In these cases the imbalance involved either only one G positive band or a G positive and a G negative band. Thus the absence of a phenotypic effect cannot always be ascribed to the deficiency in the G positive bands of coding DNA. Moreover, in some cases, the method of transmission of the chromosome abnormality was such that an imprinting effect could be postulated.

Chromosome Aberrations↗
PubMed1989

Regional assignment of the loci for adenylate kinase to 9q32 and for alpha 1-acid glycoprotein to 9q31-q32. A locus for Goltz syndrome in region 9q32-qter?

Normal levels of adenylate kinase (AK-1) and of alpha 1-acid glycoprotein (ORM1) were found in a girl with a deletion 9q32-qter secondary to a maternal translocation (4q35; 9q32), thus excluding these loci from the deleted region. These results, and comparison with other informative data, map the locus for AK-1 to 9q32 and that for ORM1 to region 9q31-q32. The girl has several signs of the Goltz syndrome (Focal dermal hypoplasia), which is listed in the McKusick catalog (no. 30560) as an X-linked dominant condition. Our finding indicates that the locus for Golz syndrome is autosomal and in region 9q32-qter or that there are two such conditions, one autosomal and one X-linked.

Adenylate Kinase↗
PubMed1989

Evidence for a human mitotic mutant with pleiotropic effect.

Male and female sibs born to third-cousin parents presented with mental retardation, microcephaly, short stature, juvenile onset limb-girdle muscular dystrophy and multiple chromosome mosaicism in lymphocytes and fibroblasts. Different aneuploidies (mostly trisomies) were found in 15-20% of the cells and trisomies for chromosome 8 and chromosome 7 predominated in lymphocytes and fibroblasts respectively, while monosomies were rare. Increased cellular death due to aneuploidy could explain symptoms such as mental and growth retardation and microcephaly. This could be an instance of an autosomal recessive mitotic mutant, possibly affecting a protein simultaneously involved in spindle apparatus and muscle function.

Abnormalities, Multiple↗
PubMed1989

Alternate centromere inactivation in a pseudodicentric (15;20)(pter;pter) associated with a progressive neurological disorder.

A 13 year old male with a severe progressive neurological disorder was found to have a pseudodicentric chromosome resulting from a telomeric fusion 15p;20p. In lymphocytes, the centromeric constriction of the abnormal chromosome was always that of the chromosome 20, while in fibroblasts both centromeres were alternately constricted. Cd staining was positive only at the active centromere, but a weak anticentromere immunofluorescence was present at the inactive one. We suggest that centromere inactivation results from a modified conformation of the functional DNA sequences preventing normal binding to centromere specific proteins. We also postulate that the patient's disorder, reminiscent of a spongy glioneuronal dystrophy as seen in Alper's and Creutzfeldt-Jakob diseases, may be secondary to the presence of the pathogenic isoform of the prion protein encoded by a gene mapped to 20p12----pter.

Adolescent↗
PubMed1988

A dominantly inherited syndrome (microcephaly, short stature, peculiar facies, mental retardation) associated with two balanced rearrangements involving chromosomes 2;7 and 5;20.

A complex balanced three-break-point rearrangement between chromosome 2 and chromosome 7 and a balanced reciprocal translocation between chromosome 5 and chromosome 20, were found associated in a girl and in her mother and grandmother. All three of them have microcephaly, low stature, peculiar asymmetric facies and slight mental retardation. We postulate that one (or more) of the five chromosome break-points disrupted one (or more) gene, leading to the expression of the syndrome and to its segregation with the chromosome rearrangement in three generation. Our finding confirms the efficiency of balanced translocations for gene mapping, althought it has led only to the exclusion mapping of all chromosomes except 2, 5, 7 and 20.

Abnormalities, Multiple↗
PubMed1988

Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome.

Instability of the heterochromatic centromeric regions of chromosomes 1, 9, and 16 associated with immunodeficiency was found in a four year old girl. Similar phenotypic and chromosomal abnormalities were described in a previous patient studied by us and in four other published cases. All these patients have facial anomalies in addition to combined immunodeficiency and chromosomal instability. Stretching of the heterochromatic centromeric regions of chromosomes 1, 16, and to a lesser extent, 9 and homologous and non-homologous associations of these regions were the most common cytogenetic findings in all the patients. Multi-branched configurations and whole arm deletions of chromosomes 1 or 16 or both were also found. Comparing clinical and chromosomal data we conclude that immunodeficiency, centromeric heterochromatin instability, and facial anomalies form a new syndrome, for which we propose the acronym ICF. A mutation interfering with the normal process of condensation of part of the centromeric heterochromatin is postulated as the basic chromosome defect in this syndrome.

Child, Preschool↗
PubMed1987

Presumptive mosaic origin of an XX/XY female with ambiguous genitalia.

A child with ambiguous genitalia had an XX/XY karyotype in all tissues examined. Analyses of 11 informative polymorphisms, both chromosomal and genetic (Rh and HLA), showed no difference between the two cell lines. It is unlikely that the child originated from fertilisation of the egg and the second polar body by two sperms; therefore, we hypothesise that the child originated from an XXY zygote after mitotic errors during cleavage. Recent findings of differences in the chromosome constitution between the extra-embryonic tissues and the fetus support this view.

Disorders of Sex Development↗
PubMed1987

Translocation X;13 in a patient with retinoblastoma.

We describe the clinical and cytogenetic findings in a child with retinoblastoma and a translocation between chromosomes X and 13. The X;13 translocation in this patient does not involve band 13q14, the assigned locus for retinoblastoma.

Chromosome Banding↗
PubMed1986

Indirect immunofluorescence of inactive centromeres as indicator of centromeric function.

Two previous single case reports from the literature showed the presence or absence of centromeric antigens at the site of the inactive centromeres in one (X;X) and in one (9;11) dicentric chromosome. We studied nine different dicentric chromosomes using anticentromeric antibodies and immunofluorescence techniques. In the four autosomal dicentrics the inactive centromere was consistently positive while the dicentrics composed of two X chromosomes were either positive or negative; one case of (X;Y) dicentric was negative. The results indicate that the X chromosome mode of replication may be involved in the suppression of immunofluorescence at the site of the inactive centromere and that one centromere of the dicentric chromosome may lose its function but conserve some of its antigenic properties. This indicates that not all these antigens play a rôle in the microtubules-centromere interaction.

Cells, Cultured↗
PubMed1986

A new chromosome instability disorder.

Chromosome analysis in a 31-year-old woman referred for primary amenorrhea, revealed a very high incidence of chromosome aberrations. She had microcephaly and immunodeficiency. Her healthy parents were consanguineous (1/32) and a younger sister, also with primary amenorrhea, died when 20 years old with a malignant lymphoma. Chromosome studies were performed on lymphocytes and fibroblasts and in both tissues a high proportion of metaphases with multiple chromosome aberrations was found. Clonal and sporadic rearrangements, consisting of balanced and unbalanced translocations and dicentric chromosomes were more numerous than chromatid and chromosome breaks. In the lymphocytes the same unbalanced translocation t(8q;21q) was present in about 59% of the metaphases. Rearrangements involving chromosomes 7 and 14, similar to those described in patients with ataxia-telangiectasia were found, but with a lower frequency. Sister Chromatid Exchanges were not increased. Chromosome and chromatid abnormalities were enhanced after exposure of cells to mitomycin C but not after exposure to the radiomimetic drug bleomycin. Clinical and cytogenetic characteristics of the patient are compared with those of syndromes (Ataxia-Telangiectasia and Werner's syndrome) or isolated cases (Weemaes et al. 1981, Sperling 1983, Spinner et al. 1985) whose features are similar to those of our patient. This case might represent a new chromosome instability syndrome due to a recessive mutation.

Adult↗
PubMed1985

Dup(3)(p2----pter) in two families, including one infant with cyclopia.

We report on 2 unrelated cases of duplication of distal 3p due to balanced maternal translocation t(3;6)(p23;q27) and t(2;3)(p25;p23) respectively. One family was ascertained through the unbalanced offspring and the other through echographic examination of the balanced carrier mother. These cases confirm that dup(3)(p2----pter) results in a characteristic syndrome with distinctive facial appearance. In family 2 inspection of a photograph of a deceased sib was sufficient to conclude that he was affected. The patient in family 2 had cyclopia. Since holoprosencephaly was also reported by Martin and Steinberg [1983], we conclude that this anomaly appears to be a sign of the syndrome. The duplication usually derives from a maternal balanced translocation, in most cases from adjacent-1 segregation. However, family 2 was ascertained through a balanced female carrier who inherited the translocation from the father. We have noted that the second chromosome (which varies without apparent preferences) involved in these translocations is broken consistently at a distal band.

Abnormalities, Multiple↗
PubMed1984

The Cd technique identifies a specific structure related to centromeric function.

The evidence that the Cd technique identifies the kinetochore was based on the finding that inactive centromeres are C-positive but Cd-negative. The identity between Cd-positivity and centromere function is now confirmed by the reverse procedure: a stable abnormal chromosome is consistently C-negative but Cd-positive at its single centromeric constriction. This demonstrates that the Cd dots are not a relic of C-banding but identify the active centromere.

Centromere↗
PubMed1984

A liveborn 69,XXX triploid. Origin, X chromosome activity and gene dosage.

A 69,XXX female liveborn triploid survived 45 days. The phenotype was consistent with the average clinical picture of liveborn triploids. Autopsy revealed slight atrophy of cerebral cortex and corpus callosum and severe adrenal hypoplasia. Chromosome polymorphisms indicated that the origin of this triploid was dispermy. Replication studies of the X chromosome performed on lymphocytes and fibroblasts showed that the majority of cells had two late replicating X chromosomes. X chromosome inactivation in spontaneous abortuses and liveborn triploids is discussed. Nine enzymes encoded by autosomal genes were tested, five had normal, three increased, and one reduced levels of activity. The reduced activity of alpha-galactosidase, an X-linked enzyme, is in agreement with cytogenetic findings and demonstrated a gene dosage effect.

Adult↗
PubMed1983

Presence of H-Y antigen in female patients with sex-chromosome mosaics and absence of testicular tissue.

H-Y antigen was tested in five women with sex chromosome mosaicism and gonadal streaks. Three patients had a 45,X/46,XY or 46,X,der(Y) and two a 45,X/46,X, der(X) chromosome constitution. All patients were H-Y antigen positive. Lack of testis differentiation in these women may be explained by subthreshold expression of H-Y antigen, different H-Y antigen molecules, and/or different tissue distribution of the chromosome mosaicism.

Adolescent↗
PubMed1983

Deficiency, transposition, and duplication of one 15q region may be alternatively associated with Prader-Willi (or a similar) syndrome. Analysis of seven cases after varying ascertainment.

Seven patients are described who have some or all of the symptoms of Prader-Willi syndrome. They were ascertained by varying criteria starting either from the clinical picture or from the identification of a chromosome abnormality involving the proximal portion of the long arm of chromosome 15. The chromosome abnormalities consisted of two balanced translocations (15;18 and 8;15), three unbalanced ones (15;18, 15;19, and 9;15), and one interstitial deletion of bands 15q11 and q12. The seventh case had an unidentified extra chromosome. These data and a review of the literature led to the conclusion that deficiency, transposition, and even duplication of the region(s) 15q11-q13 may all result in a syndrome which is identifiable with or similar to the Prader-Willi syndrome.

Adolescent↗