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Biomedical subjects

M Genuardi

Publications and source records attributed to M Genuardi.

At least 73 records · Page 4Linked to original sources
PubMed1993

Split hand/split foot anomaly in a family segregating a balanced translocation with breakpoint on 7q22.1.

An apparently balanced translocation, t(2;7)(q21.1;q22.1) was detected in a female patient with bilateral split hand and right split foot. Split hand/split foot (SHSF) segregated as an autosomal dominant character with low penetrance in her family. The translocation was present in 6 of 13 additional relatives investigated, one of whom also had split hand on right. This observation provides further confirmation of the presence of a locus for SHSF on 7q and narrows the critical region to band 7q22.1. Defects caused by alterations of this chromosome region are variable and include manifestations of both syndromal and non-syndromal SHSF. Review of SHSF cases associated with chromosome 7 abnormalities showed a preferential involvement of the lower limbs and of the right side, suggesting the action of locally restricted developmental resistance mechanisms.

Chromosome Banding↗
PubMed1993

Cerebro-reno-digital (Meckel-like) syndrome with Dandy-Walker malformation, cystic kidneys, hepatic fibrosis, and polydactyly.

We report on a boy with several findings of the Meckel syndrome, such as hepatic fibrosis, polycystic kidneys, post-axial hexadactyly, and genital abnormalities, but a Dandy-Walker malformation rather an occipital meningocele. Progressive deterioration of renal function beginning at 37 months led to death at 43 months. Both Dandy-Walker malformation and survival to the fourth year are unusual findings in Meckel syndrome. This uncommon combination represents a further demonstration of the pleiotropy/heterogeneity of the cerebro-reno-digital syndromes.

Abnormalities, Multiple↗
PubMed1993

A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease.

Complete sequencing of the prion protein open reading frame of a 68-year-old woman affected by a familial form of Creutzfeldt-Jakob disease (CJD) revealed a new mutation at codon 210 resulting in the substitution of isoleucine for valine. Moreover, a new 24-bp deletion encompassing codons 54 to 61 or 62 to 69 was found in the other allele. Four of the 17 asymptomatic relatives tested carry the 210 mutation. Two of them were 81 and 82 years old. Four of 22 patients with CJD whose recorded familial history was negative for demented illnesses, but none of 103 healthy control subjects, tested positive for the 210 mutation. These data suggest that the 210 mutation is associated with CJD, but that environmental factors or incomplete penetrance may contribute to the development of the disease. This finding also suggests that in Italy, familial CJD is more common than previously reported.

Aged↗
PubMed1993

Mapping of a gene for non-specific X linked mental retardation: evidence for linkage to chromosomal region Xp21.1-Xp22.3.

Linkage analysis of a non-specific form of X linked mental retardation (MRX) was performed with 16 polymorphic markers spanning the entire X chromosome in a three generation Italian family, including four male patients with moderate mental retardation. One obligate carrier woman had mild mental retardation and another two had normal intelligence. The results indicate tight linkage to DNA markers DXS84 (L754), DXS164 (pERT87-15), and DXS278 (CRI-S232). A maximum lod score of 2.11 at theta = 0.00 was obtained with DXS164 and DXS278. The linked region spanned chromosomal bands Xp21.1-Xp22.3, that is, the same portion of the X chromosome where MRX2 and MRX10-13 have been previously localised.

Adolescent↗
PubMed1992

Effects of dexamethasone on the growth and epidermal growth factor receptor expression of the OVCA 433 ovarian cancer cells.

We studied the correlation between dexamethasone (Dex) induced growth effects and modulation of epidermal growth factor receptor (EGFR) expression in OVCA 433 ovarian cancer cells. These cells express specific high and low affinity 125I-EGF binding sites and are growth stimulated by EGF. Dex exhibits mitoinhibitory effects by recruiting OVCA 433 cells in the G0-G1 phase of the cycle, but increases the number of both the high and the low affinity EGFR in a dose dependent manner. The maximal EGFR expression increase occurs after 24 h of Dex treatment consistently with Northern blot studies. The mitogenic activity of EGF in OVCA 433 cells is not affected by the presence of Dex. Moreover Dex growth inhibition occurs in JA1 cells, an ovarian cancer cell line which expresses unfunctional EGFR and which is unresponsive to EGF. Our results indicate that the Dex induced growth effects occur independently of EGFR expression.

Antibodies, Monoclonal↗
PubMed1992

Dosage analysis at the CSF1 and CSF1R loci in a new case of partial trisomy 5q.

We report on a new case of trisomy for the distal portion of chromosome 5q, arising from a maternal balanced translocation, t(5;22)(q33;q13). The patient presented with mental retardation and peculiar craniofacial anomalies, similar to those already described in trisomy 5q3. Overall, the phenotype bore some resemblance to that of the Brachmann-De Lange syndrome. The extent of the duplicated region was investigated through a combined molecular-cytogenetic approach, using 5q probes for gene dosage analysis by Southern blot, which allowed confirmation of breakpoint assignment to band 5q33. Since most manifestations of trisomy 5q3 are observed in patients with duplications spanning 5q34-qter, it seems that the critical sequences involved in phenotype determination lie within this very distal segment.

Adolescent↗
PubMed1991

Chronic myelogenous leukemia in the course of chronic lymphocytic leukemia: evidence for an independent clonal origin.

We report on a 69-year-old man who developed Ph-positive CML 6 years after the onset of B-cell CLL. When CML was diagnosed, both malignant cell populations were detected in bone marrow and peripheral blood. Peripheral leukocytes were fractionated by Ficoll-Hypaque density gradient, and cytogenetic and molecular studies were performed on mononuclear cell and granulocyte-enriched populations. Mononuclear cells were stimulated with either PHA or PWM. In PHA-treated cultures 76% of the metaphases were Ph-negative, while after PWM stimulation 87% were Ph-positive. A bcr rearrangement was observed in DNA from the granulocyte-enriched fraction, but not in mononuclear cells. On the contrary the IgH locus resulted in monoclonally rearranged DNA, only in peripheral blood mononuclear cells. These results indicate that the two neoplastic populations originated independently.

Aged↗
PubMed1991

Genomic changes on the short arm of human chromosome 1 in breast cancer.

A total of 38 DNA sample pairs from normal and cancerous breasts were specifically examined for alterations on the short arm of chromosome 1 using probe pYNZ2. Of the pairs, 24 (63%) displayed changes at this locus including amplifications, deletions, gene rearrangements, and altered band intensities between heterozygous alleles. Due to technical considerations, this number is likely to be a conservative estimate of the frequency of alterations in this region. When data using a different probe from the short arm of chromosome 1 was added, the overall involvement of this region increased to 73%. The combined data indicate we have localized a region, likely to be less than 85 cm in size, that is involved in the development of breast cancer.

Breast Neoplasms↗
PubMed1990

Differential expression of FRA16B in peripheral lymphocytes and bone marrow cells.

Expression of the rare fragile site FRA16B in chromosome band 16q22 was studied in bone marrow (BM) cells and peripheral blood lymphocytes (PBLs) from three unrelated subjects. Although FRA16B was detected only in PBLs from two healthy subjects who had been previously treated for non-Hodgkin's lymphoma (NHL), both cell types displayed FRA16B in a patient with chronic myelomonocytic leukemia (CMMoL). This variability in expression could be related to differences in the proliferative status of the cell populations or to differences in gene activity in the fragile site region.

Adult↗
PubMed1990

Analysis of 138 consecutive ovarian cancer patients: incidence and characteristics of familial cases.

Eight families with two or more first-degree relatives affected with ovarian carcinoma were identified among a series of 138 consecutive ovarian cancer patients. History of breast cancer was reported in six of the eight families. Five of 19 patients with familial cancer developed ovarian cancer as a second primary tumor following breast carcinoma, whereas only 6/130 sporadic cases had a previous history of breast cancer. No significant difference was detected in clinical and pathological features between sporadic and familial cases. However, in three high-risk families ovarian cancer tended to develop at a younger age compared with other familial cases and with sporadic occurrences, and nulliparity was less frequent in the familial group. These observations emphasize the need to take into account multiple factors-in addition to positive family history-for the evaluation of genetic predisposition to ovarian carcinoma.

Carcinoma↗
PubMed1990

Brachy/ectrodactyly and absence or hypoplasia of the fibula: an autosomal dominant condition with low penetrance and variable expressivity.

A complex dysostosis characterized by brachy- and/or ectrodactyly and fibular hypoplasia was found in two distantly related individuals. The proposita, aged 25 years, showed metacarpal and phalangeal hypoplasia on both hands, ectrodactyly on both feet, and nearly complete bilateral absence of the fibula. Only milder acromelic defects were detected in a second cousin. A similar pattern of skeletal involvement had been previously described in an unrelated Italian family. The peculiar segregation pattern can be explained by autosomal dominant inheritance with low penetrance and variable expressivity.

Abnormalities, Multiple↗
PubMed1989

Distal deletion of chromosome Ip in ductal carcinoma of the breast.

By use of recombinant DNA probes that correspond to genetic loci residing on human chromosome 1, DNA samples from 37 ductal breast carcinomas and constitutional DNA from the same individuals were tested for loss of heterozygosity. A high frequency (41%) of reduction to homozygosity was detected with the probe p1-79, which recognizes the highly polymorphic locus D1Z2, localized on 1p36. Loss of heterozygosity at other chromosome 1 loci was much less common, not exceeding a frequency of 10%, and was never observed in the absence of the D1Z2 loss. Somatic loss of heterozygosity at D1Z2 was more frequent in patients with a strong family history of breast cancer (60%), in patients with early diagnosis (before 45 years of age) (70%), and in those with multiple tumors or tumor foci (50%) than in patients with none of the characteristics of hereditary tumors (21%). No associations were observed between loss of heterozygosity and prognostic factors. These results suggest that inactivation of a tumor suppressor gene located on the distal portion of chromosome 1p, alone or combined with other genetic changes, may represent a fundamental step in the pathogenesis of ductal carcinoma of the breast.

Adult↗
PubMed1988

Long-term cytogenetic effects of antineoplastic treatment in relation to secondary leukemia.

Chromosome translocations are consistently present in leukemias and lymphomas and are likely to represent primary events in the development of these neoplasias. A study of conditions that predispose to leukemia could shed some light on the origin of these translocations and therefore help in clarifying their exact role in the process of neoplastic transformation. Based on this assumption, we studied a group of individuals treated with radiochemotherapy for previous lymphoma and who were at increased risk of developing a secondary leukemia. The group comprised 14 Hodgkin's disease patients, 11 non-Hodgkin's lymphoma patients, and 13 controls. The patients were in remission and had been off therapy for at least 6 months. Chromosomes were studied from phytohemagglutinin (PHA)-stimulated peripheral lymphocytes and from bone marrow cells by the direct method and after short-term cultures (72 hours). The latter were also exposed to 5-bromodeoxyuridine (BrdU). Metaphases were scored for chromosome breaks, gaps, and other rearrangements. The percentage of gaps and breaks was significantly higher in patients than in controls. The difference was induced by BrdU and was apparent in bone marrow cells, but not in peripheral lymphocytes. We conclude that individuals exposed to the action of mutagenic agents (radiochemotherapy) have an increased chromosome instability that could be related to their increased risk of developing a secondary leukemia.

Adolescent↗