RESUMO
Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.
Assuntos
Aberrações Cromossômicas , Aconselhamento Genético , Predisposição Genética para Doença , Prognóstico , Adulto , Hibridização Genômica Comparativa , Feminino , França , Estudos de Associação Genética , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Gravidez , Diagnóstico Pré-Natal , Estudos Prospectivos , Risco , Suíça , Adulto JovemRESUMO
The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.
Assuntos
Neoplasias Hematológicas/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Translocação Genética/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Citogenética , Feminino , França , Proteínas de Homeodomínio/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Pessoa de Meia-Idade , Receptores Citoplasmáticos e Nucleares/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Sociedades MédicasRESUMO
Reaching an accurate diagnosis in children with mental retardation associated or not with dysmorphic signs is important to make precise diagnosis of a syndrome and for genetic counseling. A female case with severe growth and development delay, dysmorphic features and feeding disorder is presented. Antenataly, the fetus was observed to have increased nuchal translucency and a slight hypoplastic cerebellum. A standard karyotype was normal. RES and a submicroscopic unbalanced subtelomeric translocation t(2p; 10q) were demonstrated after birth. We show that within the framework of a collaborative approach, a concerted research of submicroscopic subtelomeric rearrangements should be performed in case of mental retardation associated with facial dysmorphic features, and when other etiologies or non-genetic factors (iatrogenic, toxic, infectious, metabolic...) have been ruled out.
Assuntos
Transtornos Cromossômicos/genética , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 2 , Deficiência Intelectual/genética , Rombencéfalo/anormalidades , Translocação Genética , Cerebelo/anormalidades , Desenvolvimento Infantil , Pré-Escolar , Bandeamento Cromossômico , Transtornos da Alimentação e da Ingestão de Alimentos/genética , Feminino , Feto/anormalidades , Humanos , Hibridização in Situ Fluorescente , Lactente , Deficiência Intelectual/sangue , Cariotipagem , Imageamento por Ressonância Magnética , Medição da Translucência Nucal , Telômero/genéticaRESUMO
Balanced complex chromosomal rearrangements (BCCR) encompass a heterogeneous group of rare chromosomal aberrations. In this paper, we report three cases of BCCRs. In two the probands were referred for either genetic counseling or prenatal management. One case was ascertained after chromosome analysis performed because of psychiatric manifestations; this was an isolated finding. We also outline the molecular cytogenetic techniques, which were essential in confirming and precisely delineating the BCCRs identified in these patients. In addition the various aspects of genetic counseling for this type of chromosomal rearrangement, highlighting the details particular to each individual case are discussed. We discuss the classification for this type of chromosomal mutation.
Assuntos
Anormalidades Múltiplas/genética , Transtorno Autístico/genética , Quebra Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos/ultraestrutura , Transtornos Psicomotores/genética , Aborto Habitual/genética , Adulto , Criança , Pré-Escolar , Coloração Cromossômica , Cromossomos Humanos/genética , Feminino , Aconselhamento Genético , Humanos , Masculino , Modelos Genéticos , Mutagênese Insercional , Hibridização de Ácido Nucleico , Translocação GenéticaRESUMO
We describe a subtle translocation t(8;11)(p23.2;p15.5) ascertained after two induced abortions in the same sibship because of the discovery of fetal hydrops on ultrasound examination. Initial cytogenetic studies performed on cultured amniotic fluid cells were considered as normal in both fetuses. High resolution banding analysis and FISH studies performed on the parents' chromosomes revealed a paternal translocation t(8;11)(p23.2;p15.5). Retrospective FISH analysis of both fetuses showed that they carried the same chromosomal imbalance including a distal monosomy 8pter and a distal trisomy 11pter. The phenotypes of the fetuses were re-examined and found to be compatible with Beckwith-Wiedemann syndromes (BWS). FISH analysis using an IGF2 probe demonstrated the presence of three copies of the IGF2 gene. This study highlights the value of searching for subtle chromosome rearrangements in families with recurrent unexplained multiple malformation syndromes discovered prenatally. Also, it contributes to a better delineation of the prenatal phenotype of BWS. Finally, it sheds new light on the aetiology of non-immune hydrops fetalis.