RESUMO
A precise guideline establishing chromosomal microarray analysis (CMA) applications and platforms in the prenatal setting does not exist. The controversial question is whether CMA technologies can or should soon replace standard karyotyping in prenatal diagnostic practice. A review of the recent literature and survey of the knowledge and experience of all members of the Italian Society of Human Genetics (SIGU) Committee were carried out in order to propose recommendations for the use of CMA in prenatal testing. The analysis of datasets reported in the medical literature showed a considerable 6.4% incidence of pathogenic copy number variations (CNVs) in the group of pregnancies with sonographically detected fetal abnormalities and normal karyotype. The reported CNVs are likely to have a relevant role in terms of nosology for the fetus and in the assessment of reproductive risk for the couple. Estimation of the frequency of copy number variations of uncertain significance (VOUS) varied depending on the different CMA platforms used, ranging from 0-4%, obtained using targeted arrays, to 9-12%, obtained using high-resolution whole genome single nucleotide polymorphism (SNP) arrays. CMA analysis can be considered a second-tier diagnostic test to be used after standard karyotyping in selected groups of pregnancies, namely those with single (apparently isolated) or multiple ultrasound fetal abnormalities, those with chromosomal rearrangements, even if apparently balanced, and those with supernumerary marker chromosomes.
Assuntos
Transtornos Cromossômicos/genética , Análise Citogenética/métodos , Análise em Microsséries/métodos , Diagnóstico Pré-Natal/métodos , Transtornos Cromossômicos/diagnóstico , Análise Citogenética/tendências , Feminino , Humanos , Itália , Polimorfismo de Nucleotídeo Único , GravidezRESUMO
The Child Hearing Early Assessment Programme (CHEAP) regional project, was a combined departmental approach (Audiology, Neonatology) of the University Hospital of Ferrara, aimed at identifying neonatal hearing impairment and defining early intervention strategies. Aims of this project have been: (i) construction of a neonatal screening programme using evoked otoacoustic emission and auditory brainstem responses; (ii) the calculation of a precise estimate of cost-benefits for every child tested; (iii) the development of an information flow instrument (database) for the storage of data and the statistical analysis of the results. The present report refers only to the results of the project related to the otoacoustic emission data from well-babies and intensive care unit residents. In the period January 2000-December 2004, 4269 full-term newborns and 654 Neonatal Intensive Care Unit babies were tested at the Neonatology Department. The cost of the Universal Neonatal Hearing Screening was estimated at Euro 9.20 per child, considering the use of the ILO-292 apparatus, and Euro 8.28 per child in the case of an automatic screener. In this screening model, the initial hardware costs can be re-iterated into budget in a period of two years, if 1000 children per year are tested.
Assuntos
Transtornos da Audição/epidemiologia , Triagem Neonatal , Custos e Análise de Custo , Transtornos da Audição/diagnóstico , Transtornos da Audição/economia , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Triagem Neonatal/economiaRESUMO
Fetal DNA was recovered from 17 of 39 (44%) transcervical cell (TCC) samples obtained between 7 and 9 weeks of gestation by endocervical canal flushing. Trophoblast retrieval was adequate for polymerase chain reaction (PCR) amplification of Y chromosome-specific DNA sequences and detection of paternal-specific microsatellite alleles. The fetal sex predicted by PCR in TCCs was confirmed in all cases by karyotype analysis of chorionic villi at 10 weeks of gestation. The absence of the disease-associated paternal alleles in TCC samples from two pregnancies at risk for spinal muscular atrophy and myotonic dystrophy predicted unaffected fetuses in agreement with subsequent results on chorionic villi and newborns' leukocytes. A trisomy 21 fetus was diagnosed in TCCs using fluorescent in situ hybridization (FISH) and semi-quantitative PCR analysis of superoxide dismutase-1 (SOD 1). Present experience indicates that TCC sampling is a promising technique for early prenatal monitoring of Mendelian disorders and chromosome aneuploidy.
Assuntos
Reação em Cadeia da Polimerase/métodos , Diagnóstico Pré-Natal/métodos , Trofoblastos/citologia , Adulto , Colo do Útero/citologia , DNA/análise , DNA/sangue , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Atrofia Muscular Espinal/diagnóstico , Distrofia Miotônica/diagnóstico , Gravidez , Primeiro Trimestre da Gravidez , Sensibilidade e Especificidade , Análise para Determinação do Sexo/métodos , Superóxido Dismutase/genética , Irrigação Terapêutica , Cromossomo YRESUMO
The planning and evaluation of human cytogenetic studies should contemplate various confounders and effect modifiers, among these, sex and sex-related factors. The association between this variable and cytogenetic damage has been extensively studied, but conclusive evidence has thus far not been reached, especially for the most recent assays, such as the micronucleus test (MN). In the attempt to quantitatively estimate the sex effect on sister chromatid exchange (SCE), chromosomal aberration (CA), and MN in peripheral blood lymphocytes, we reanalyzed the original data sets of several biomonitoring studies performed over the last decades in 10 Italian laboratories. This approach yielded a very large database, namely 2140, 2495, and 2131 subjects screened for SCE, CA, and MN, respectively. Differences between sexes were expressed in terms of relative risk (RR) of females versus males, after adjustment for age, smoking habits, occupation exposure and inter- and intralaboratory variation. No difference between sexes was found for the frequency of SCE [RR = 1.01; 95% confidence interval (CI) = 0.99-1.03] and CA (RR = 1.00; 95% CI = 0.92-1.08) even if the CI of the RR for SCE includes the 3% excess in females frequently reported by the literature. Conversely, a 29% overall increase of the MN rate in females was observed in the whole data set (RR = 1.29; 95% CI = 1.20-1.38). Different trends by age of the MN rate are described in the two sexes, focusing on the peak observed in females in the menopausal period and on the subsequent decrease.
Assuntos
Aberrações Cromossômicas , Caracteres Sexuais , Troca de Cromátide Irmã , Adulto , Fatores Etários , Idoso , Aberrações Cromossômicas/fisiologia , Intervalos de Confiança , Citogenética , Feminino , Humanos , Modelos Lineares , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Distribuição de Poisson , Fatores Sexuais , Troca de Cromátide Irmã/fisiologiaRESUMO
To investigate the existence of an association between the frequency of chromosome aberrations (CA) in non-target tissues and cancer risk, a historical cohort study was carried out in a group of 1455 subjects screened for CA over the last 20 years in Italy. Statistically significant increases in standardized mortality ratio (SMR) for all cancers were found in subjects with medium and high levels of CA in peripheral blood lymphocytes (SMR = 178.5 and SMR = 182.0, respectively) and in subjects with high levels of CA for respiratory tract cancers (SMR = 250.8) and lymphatic and hematopoietic tissue neoplasms (SMR = 548.8). Significant trends in the SMRs were observed for these latter causes of death.
Assuntos
Aberrações Cromossômicas , Linfócitos/ultraestrutura , Neoplasias/epidemiologia , Neoplasias/genética , Estudos de Coortes , Humanos , Itália/epidemiologia , Fatores de Risco , Fatores de TempoRESUMO
Ten patients with inverted duplication of 8p (inv dup 8p) were studied with cytogenetic, biochemical and molecular techniques. The duplication for the region 8p12-p22 was always associated with a deletion of the locus D8S7 (mapped in 8p23.1) as demonstrated with the probe pSW50 by both in situ hybridization and Southern blot. Restriction fragment length polymorphisms detected by probes pSW50 (1 case) and by pG2LPL35 (locus LPL) (two cases) were informative as to a maternal origin of the anomaly. The activity of glutathione reductase, whose gene maps in the duplicated region at 8p21.1, was increased in all patients. The recognizable phenotype of inv dup 8p includes neonatal hypotonia, prominent forehead, large mouth with everted lower lip, abnormally shaped large ears, brain malformations and severe mental retardation. Our findings indicate that the chromosome rearrangement is homogeneous at least for the presence of the deletion and support the hypothesis of a common mechanism of origin.
Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas/genética , Deleção Cromossômica , Cromossomos Humanos Par 8 , Família Multigênica/genética , Anormalidades Múltiplas/enzimologia , Adulto , Southern Blotting , Aberrações Cromossômicas/enzimologia , Transtornos Cromossômicos , DNA/análise , Feminino , Rearranjo Gênico/genética , Glutationa Redutase/genética , Glutationa Redutase/metabolismo , Humanos , Hibridização In Situ , Lactente , Cariotipagem , Masculino , Polimorfismo de Fragmento de RestriçãoRESUMO
Cytogenetic and molecular analyses were carried out in two fetuses with de novo non mosaic dic (Y)(q11.2) and Yqsat. Molecular deletion of the region to which the AZF locus has been assigned was found in the first case.
Assuntos
Deleção de Genes , Oligospermia/genética , Cromossomo Y , Adulto , Amniocentese , Bandeamento Cromossômico , Mapeamento Cromossômico , Sondas de DNA , Feminino , Rearranjo Gênico , Humanos , Masculino , Reação em Cadeia da Polimerase , Gravidez , Segundo Trimestre da Gravidez , Aberrações dos Cromossomos Sexuais/diagnósticoRESUMO
We report on a case of trisomy 8 mosaicism detected prenatally in a single clone of amniotic fluid culture, and confirmed on fetal blood and on peripheral lymphocytes after birth. A follow-up was performed over 3 years, showing a clinically normal female with cognitive, neuropsychological, and linguistic development in a normal range.
Assuntos
Amniocentese , Cromossomos Humanos Par 8 , Mosaicismo , Trissomia , Pré-Escolar , Feminino , Seguimentos , Humanos , Fenótipo , GravidezAssuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 16 , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Linhagem , Diagnóstico Pré-NatalAssuntos
Anormalidades Múltiplas/diagnóstico , Neoplasias do Ventrículo Cerebral/diagnóstico , Plexo Corióideo , Aberrações Cromossômicas/diagnóstico , Cromossomos Humanos Par 18 , Cistos/diagnóstico , Doenças Fetais/diagnóstico , Diagnóstico Pré-Natal , Trissomia , Anormalidades Múltiplas/epidemiologia , Neoplasias do Ventrículo Cerebral/epidemiologia , Aberrações Cromossômicas/epidemiologia , Transtornos Cromossômicos , Cistos/epidemiologia , Feminino , Doenças Fetais/epidemiologia , Humanos , Itália/epidemiologia , Gravidez , Estudos ProspectivosAssuntos
Cromossomos Humanos Par 8 , Cariotipagem , Mosaicismo , Trissomia , Adulto , Feminino , Humanos , Gravidez , Segundo Trimestre da GravidezRESUMO
A new endoscopic technique for chorion biopsy is presented. The significance of stereomicroscopy by learning morphological features of chorionic tissue is stressed.
Assuntos
Vilosidades Coriônicas/patologia , Diagnóstico Pré-Natal , Biópsia , Feminino , Humanos , Microscopia/métodos , Gravidez , Primeiro Trimestre da GravidezAssuntos
Indústria Química , Troca de Cromátide Irmã/efeitos dos fármacos , Estirenos/farmacologia , Adolescente , Adulto , Poluentes Ocupacionais do Ar/análise , Aberrações Cromossômicas , Feminino , Glioxilatos/urina , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/ultraestrutura , Masculino , Ácidos Mandélicos/urina , Pessoa de Meia-Idade , Estireno , Estirenos/metabolismoRESUMO
Few studies exist about chromosomal damage in workers occupationally exposed to styrene. In the present study, chromosomal aberrations and SCEs were analyzed from cultures of peripheral lymphocytes of workers employed in 6 different reinforced-plastics industries with styrene air exposure levels ranging from 30 to 400 mg/mc. A control group was selected on the base of sex, age and smoking habit. We examined 50-h cultures (for chromosomal-aberrations) and 72-h cultures (for SCEs) for each individual. All workers exposed to styrene, as compared with controls, showed significantly increased frequencies of chromosomal aberrations, while SCEs were significantly increased at 4 of the 6 plants. High SCE values appeared with styrene air concentrations higher than 200 mg/mc. Apart from the possible presence and role of other interfering chemicals in the various plants, chromosomal aberrations seem to be more sensitive than SCEs for the detection of chromosomal damage caused by exposure to low doses of styrene.
Assuntos
Aberrações Cromossômicas/efeitos dos fármacos , Troca Genética/efeitos dos fármacos , Troca de Cromátide Irmã/efeitos dos fármacos , Estirenos/farmacologia , Exposição Ambiental , Humanos , Linfócitos/ultraestruturaRESUMO
One thousand coronary arteriography performed in the catheterization laboratory of the Department of Cardiology (University of Padua) from 1973 to 1978 were reviewed. Indication to perform a coronary arteriography was established in 668 patients with clinically suspected coronary artery disease and in 332 patients affected by different heart disease in whom the study of coronary arteries was judged to be usefull. The percutaneous technique was usually employed. The overall mortality rate was 0.2%; there were no death in the last three years. The overall morbility was 3.5% (2.3 from 1976 to 1978). The anterior descending artery appeared to be the most frequently and precociously affected area. There was a good correlation between severity of the atherosclerotic lesions and age or sex of the patients. We could recognize coronary disease, when present, on the basis of clinical evaluation in patients without different heart disease.