Asunto(s)
Fusión Génica , Proteína HMGB3/genética , Proteínas de Complejo Poro Nuclear/genética , Animales , Proteínas de Homeodominio/genética , Humanos , Ratones , Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide , Proteínas de Neoplasias/genética , Oncogenes , Retroviridae/genética , Transducción GenéticaRESUMEN
OBJECTIVE: X inactivation pattern in X chromosome rearrangements usually favor the less unbalanced cells. It is correlated to a normal phenotype, small size or infertility. We studied the correlation between phenotype and X inactivation ratio in patients with X structural anomalies. PATIENTS AND METHODS: During the 1999-2005 period, 12 X chromosome rearrangements, including three prenatal cases, were diagnosed in the Laboratoire de Cytogénétique of Strasbourg. In seven cases, X inactivation ratio could be assessed by late replication or methylation assay. RESULTS: In three of seven cases (del Xp, dup Xp, t(X;A)), X inactivation ratio and phenotype were consistent. The four other cases showed discrepancies between phenotype and X inactivation pattern: mental retardation and dysmorphism in a case of balanced X-autosome translocation, schizophrenia and autism in two cases of XX maleness and MLS syndrome (microphthalmia with linear skin defects) in a case of Xp(21.3-pter) deletion. CONCLUSION: Discrepancies between X inactivation ratio and phenotype are not rare and can be due to gene disruption, position effect, complex microrearrangements, variable pattern of X inactivation in different tissues or fortuitous association. In this context, the prognostic value of X inactivation study in prenatal diagnosis will be discussed.
Asunto(s)
Cromosomas Humanos X/genética , Metilación de ADN , Momento de Replicación del ADN , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Inactivación del Cromosoma X , Anomalías Múltiples/genética , Adulto , Trastorno Autístico/genética , Preescolar , Deleción Cromosómica , Enanismo/genética , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Genes Ligados a X , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/embriología , Humanos , Recién Nacido , Masculino , Discapacidad Intelectual Ligada al Cromosoma X/genética , Fenotipo , Diagnóstico Prenatal , Receptores Androgénicos/genética , Esquizofrenia/genética , Translocación Genética/genética , Síndrome de Turner/genéticaRESUMEN
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.
Asunto(s)
Neoplasias Hematológicas/genética , Proteínas de Complejo Poro Nuclear/genética , Translocación Genética/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Análisis Citogenético , Femenino , Francia , Proteínas de Homeodominio/genética , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Persona de Mediana Edad , Receptores Citoplasmáticos y Nucleares/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Sociedades MédicasRESUMEN
We report the case of a boy whose karyotype at birth showed additional material on one chromosome 15. He underwent treatment for unilateral nephroblastoma at 6 years old. At 23 years old, he presented with body asymmetry, facial dysmorphism, arachnodactyly, severe scoliosis, and mental retardation. Molecular cytogenetic analyses of peripheral lymphocytes demonstrated a complex mosaic with three clones. A major cell lineage (68%) showed a chromosome 15 with additional material fused to its telomere long arm that was constituted by an inverted duplicated 15q24.3-qter segment. Therefore, the resulting add(15)(q) harbored an intrachromosomal triplication with the middle segment being inverted in orientation. A minor cell lineage (7%) showed an abnormal chromosome 3 resulting from a telomeric fusion between its short arm and an inverted duplicated 15q24.3-qter segment. The third cell lineage (25%) showed a normal 46,XY constitution. Finally, this resulted in tetrasomy for the distal 15q24.3-qter region in 75% of the patient's lymphocytes. To our knowledge, distal 15q tetrasomy is rare and only eight cases have been reported in the literature, all due to a supernumerary analphoid marker consisting of an inverted duplication. We report here the first observation of distal 15q tetrasomy associated with a 46 chromosomes constitution. We compare the phenotype of our patient to previous cases of distal tetrasomy 15q and discuss the mechanisms underlying this chromosomal rearrangement.
Asunto(s)
Anomalías Múltiples/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 15/genética , Anomalías Múltiples/patología , Adulto , Niño , Bandeo Cromosómico , Cara/anomalías , Estudios de Seguimiento , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Discapacidad Intelectual/patología , Cariotipificación , Masculino , Mosaicismo , Fenotipo , Escoliosis/patología , Tumor de Wilms/patologíaRESUMEN
Prenatal diagnosis of a true fetal tetraploidy in direct and cultured chorionic villi: Tetraploidy is characterized by four complete sets of chromosomes (4n= 92). Although it has been frequently reported in spontaneous abortions, tetraploidy is extremely rare in term pregnancy. Most of late surviving patients are diploid/tetraploid mosaics and present severe mental and physical impairment. Up to date, only five tetraploidies were ascertained in the prenatal stage in amniocytes and/or fetal blood lymphocytes. No one has been reported in chorionic villi probably because tetraploidy is generally considered in this tissue as a false positive result due to confined placental mosaicism (CPM) or placental culture artefacts. We report here on a case of tetraploidy detected in chorionic villi because of fetal cystic hygroma. We discuss the reliability of this diagnosis and propose guidelines in the follow-up of tetraploidies detected after chorionic villus sampling (CVS). Thus a misdiagnosis of this poor condition will be avoided at best and an appropriate genetic counseling will be given to the parents.
Asunto(s)
Muestra de la Vellosidad Coriónica , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/genética , Poliploidía , Amniocentesis , Aberraciones Cromosómicas , Resultado Fatal , Femenino , Enfermedades Fetales/diagnóstico por imagen , Guías como Asunto , Humanos , Cariotipificación , Linfangioma Quístico/diagnóstico , Linfangioma Quístico/embriología , Linfangioma Quístico/genética , Masculino , Mosaicismo , Placenta/citología , Embarazo , Complicaciones del Embarazo , Reproducibilidad de los Resultados , UltrasonografíaRESUMEN
We report on two male siblings with partial trisomy 2p22-pter and partial monosomy 15q26-qter resulting from a maternally derived translocation t(2;15)(p22;q26). Both fetuses had different neural tube defects (craniorachischisis in the first fetus and anencephaly in the second fetus) which were detected by sonographic examination at the end of the first trimester of pregnancy. This report demonstrates the importance of chromosomal analysis in the etiologic exploration of neural tube defects and supports the importance of 2p24 triplication in neural tube development.
