Assuntos
Deficiência Intelectual/genética , Isoleucina-tRNA Ligase/genética , Hepatopatias/genética , Hipotonia Muscular/genética , Adulto , Criança , Pré-Escolar , Feminino , Genes Recessivos/genética , Predisposição Genética para Doença , Humanos , Deficiência Intelectual/patologia , Hepatopatias/patologia , Masculino , Hipotonia Muscular/patologia , Mutação/genéticaRESUMO
Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 account for a significant proportion of hereditary non-polyposis colorectal cancer (HNPCC) families. One approach by which development of an efficient DNA-testing procedure can be implemented is to describe the nature and frequency of common mutations in particular ethnic groups. Two hundred and twenty-six patients from families matching the Amsterdam II diagnostic criteria or suspected HNPCC criteria were screened for MSH2 and MLH1 germline mutations. Fifty different pathogenic mutations were found, 25 in MSH2 and 25 in MLH1. Twenty-four of these had not previously been described in other populations. Among our 78 families with MSH2 or MLH1 mutations, 54 (69.2%) were affected by recurrent mutations including 38 found at least twice in our own series. Two of the most frequent alterations were a substitution of A to T at the splice donor site of intron 5 of MSH2 and a missense change (A681T) of MLH1 found in 10 and eight families, respectively. Among large deletions detected by the multiplex ligation-dependent probe amplification assay, exon 9 deletions in the MSH2 gene were found in two families. Our results indicate that a screening protocol specific for the Polish population that is limited to the detection of all reported mutations will result in the identification of the majority of changes present in MLH1 and MSH2 genes in Polish HNPCC kindreds.
Assuntos
Proteínas de Transporte/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Mutação em Linhagem Germinativa , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Proteínas Adaptadoras de Transdução de Sinal , Sequência de Bases , Estudos de Coortes , Análise Mutacional de DNA/métodos , Saúde da Família , Feminino , Humanos , Reação em Cadeia da Ligase/métodos , Masculino , Dados de Sequência Molecular , Proteína 1 Homóloga a MutL , PolôniaRESUMO
Individual sensitivity to mutagens has been considered to play an important role in head-and-neck squamous cells carcinoma (HNSCC) development. The bleomycin test was introduced for establishing constitutional susceptibility to mutagens (T.C. Hsu, D.A. Johnston, L.M. Cherry, D. Ramkisson, S.P. Schantz, J.M. Jessup, R.J. Winn, L. Shirley, C. Furlong, Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis, Int. J. Cancer 43 (1989) 403-409). Its criteria are based on scoring of chromosome aberrations (CAs, mainly breaks) in Giemsa-stained chromosomes. Fluorescence in situ hybridization (FISH) offers an easy method for analysis of translocations, acentric fragments and dicentrics. In the present study FISH was applied in the analysis of bleomycin-induced CAs of the HNSCC patients and controls. The results proved that FISH is a complementary method to the classical staining in monitoring of bleomycin-induced CAs.
Assuntos
Bleomicina/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Aberrações Cromossômicas , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Hibridização in Situ Fluorescente , Adulto , Idoso , Corantes Azur , Estudos de Casos e Controles , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 5 , Dano ao DNA , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Congenital malformation syndromes are often caused by unbalanced chromosome translocations, which appear spontaneously or may be inherited from a healthy parent being the carrier of a balanced reciprocal translocation (rcp). Breakpoints, underlying chromosome fragment exchanges, may be located at any point of any chromosome and therefore, an infinite number of different translocations is possible. Special emphasis is placed both on the clinical characterization of every rare chromosomal aberration syndrome and on the determination of its breakpoints. OBJECTIVES: Diagnosis of a 8q22-->qter duplication in a child with multiple congenital malformations. MATERIAL AND METHODS: We determined the karyotypes of the five members of proband's family were established by using classical cytogenetic methods on whole blood obtained by venipuncture. RESULTS: We described a rare familial reciprocal translocation t(8; 14), observed in balanced form in mother and one healthy son, while being unbalanced in the son with congenital malformations. CONCLUSIONS: Balanced chromosome 8 aberration carriers should be aware of the procreation risks and need genetic counseling.
Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 8/genética , Translocação Genética , Anormalidades Múltiplas/patologia , Cromossomos Humanos Par 14/genética , Ossos Faciais/anormalidades , Feminino , Genitália Masculina/anormalidades , Humanos , Lactente , Cariotipagem , Masculino , LinhagemRESUMO
The genotoxic properties of diepoxybutane (DEB) have been extensively studied by many authors. The most often investigated endpoints were sister chromatid exchanges (SCE) and micronuclei (MN), and less frequently, chromosome aberrations (CAs). In the present study, the analysis of CAs induced by DEB in vitro on human whole blood lymphocytes was performed by using three methods of chromosome visualisation: Giemsa-staining, GTG banding and chromosome painting (FISH). The results showed that DEB is a very efficient clastogenic agent and induces chromosome breaks and gaps as well as tri- and quadriradials (observed by using classical cytogenetic methods) together with acentrics (observed by using FISH) on the statistically significant level, as compared to controls (chi2-test, p<10-5). The analysis of GTG-banded metaphases revealed that the break-points were distributed non-randomly within the chromosomes and located mainly in 1p, 1q, 2p, 2p, 6q, 9q and 14q (p<10-6). In conclusion it can be stated, that methods applied in this work are complementary and can be used successfully for estimation of the clastogenic potential of the tested chemical.
