RESUMEN
Genet Med 19 3, 294-296.
Asunto(s)
Genética Médica/educación , Genómica/educación , Humanos , Laboratorios , Consejos de Especialidades/normas , Estados UnidosRESUMEN
Trisomy 22 is the third most common autosomal trisomy occurring in about 0.4% of all clinically recognized pregnancies. Complete non-mosaic trisomy 22 is extremely rare in live births. Most affected children die before one year of age. To date, only 29 liveborn cases have been reported and none has carried an additional genetic lesion. In this report, we describe the clinical presentation, cytogenetic, and cytogenomic findings in a liveborn female with complete non-mosaic trisomy 22 as well as a paternally inherited, balanced reciprocal chromosomal rearrangement t(4;6)(q33;q23.3). The proband manifested features commonly seen in individuals with non-mosaic trisomy 22 such as intrauterine growth retardation (IUGR), single umbilical artery, cranial abnormalities, short neck, cleft lip and palate, dysmorphic ears, hypoplastic nipples, digital malformation, congenital heart defects, dysplastic kidneys, and genital anomalies. In addition, she had lobar holoprosencephaly, aqueductal stenosis, and limb and eye problems that have not been associated with complete trisomy 22 in previous reports. She died at 35 days of age of complex heart disease and renal failure. We are hereby expanding the cytogenetic and clinical spectrum of this rare chromosome disorder. Clinical features of liveborn children with non-mosaic trisomy 22 are reviewed and compared to those in our proband. The impact of genomic content in relation to the survival of trisomies in humans is also discussed.
Asunto(s)
Anomalías Múltiples/genética , Anomalías Múltiples/patología , Cromosomas Humanos Par 4/genética , Cromosomas Humanos Par 6/genética , Translocación Genética/genética , Trisomía/genética , Trisomía/patología , Cromosomas Humanos Par 22/genética , Análisis Citogenético , Resultado Fatal , Femenino , Humanos , CariotipificaciónRESUMEN
Rhabdomyosarcoma is the most common pediatric soft tissue malignancy. Two major subtypes, alveolar rhabdomyosarcoma and embryonal rhabdomyosarcoma, constitute 20 and 60% of all cases, respectively. Approximately 80% of alveolar rhabdomyosarcoma carry two signature chromosomal translocations, t(2;13)(q35;q14) resulting in PAX3-FOXO1 fusion, and t(1;13)(p36;q14) resulting in PAX7-FOXO1 fusion. Whether the remaining cases are truly negative for gene fusion has been questioned. We are reporting the case of a 9-month-old girl with a metastatic neck mass diagnosed histologically as solid variant alveolar rhabdomyosarcoma. Chromosome analysis showed a t(8;13;9)(p11.2;q14;9q32) three-way translocation as the sole clonal aberration. Fluorescent in situ hybridization (FISH) demonstrated a rearrangement at the FOXO1 locus and an amplification of its centromeric region. Single-nucleotide polymorphism-based microarray analysis illustrated a co-amplification of the FOXO1 gene at 13q14 and the FGFR1 gene at 8p12p11.2, suggesting formation and amplification of a chimerical FOXO1-FGFR1 gene. This is the first report to identify a novel fusion partner FGFR1 for the known anchor gene FOXO1 in alveolar rhabdomyosarcoma.
Asunto(s)
Factores de Transcripción Forkhead/genética , Amplificación de Genes , Fusión Génica , Neoplasias de Cabeza y Cuello/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Rabdomiosarcoma Alveolar/genética , Cromosomas Humanos Par 13 , Cromosomas Humanos Par 8 , Cromosomas Humanos Par 9 , Análisis Citogenético , Femenino , Proteína Forkhead Box O1 , Neoplasias de Cabeza y Cuello/patología , Humanos , Hibridación Fluorescente in Situ , Lactante , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Rabdomiosarcoma Alveolar/secundario , Translocación GenéticaRESUMEN
We report the unique association of variable constitutional mosaicism 46,X, i(X)(p10)/46,XX with recurrent thrombocytopenia in a child with failure to thrive and apnea in infancy. Her bone marrow had equal distribution of the normal and abnormal cell lines at diagnosis, at nearly 6 years of age. Improvement of her pancytopenia and thrombocytopenia was concurrent with a decreasing level of mosaicism observed in multiple studies over the next 3 years. This suggests that extra copies of genes on the p-arm are inhibitory to blood cell maturation, with long-term selection against the i(Xp)-containing cells.
Asunto(s)
Cromosomas Humanos X/genética , Isocromosomas/genética , Mosaicismo , Pancitopenia/complicaciones , Pancitopenia/genética , Trombocitopenia/complicaciones , Trombocitopenia/genética , Niño , Preescolar , Femenino , Humanos , CariotipificaciónRESUMEN
We describe the rare finding of a 33-month-old child neonatally diagnosed with Down syndrome, who presented with pre-B acute lymphoblastic leukemia (ALL) with a pretreatment bone marrow karyotype in which a low hypodiploid cell line (38 chromosomes) was identified in 17/19 cells studied. The abnormal cell line retained the extra constitutional chromosome 21. Hypodiploidy (loss of one or more chromosomes) is seen in approximately 5% of all childhood pre-B ALL cases and in approximately 2.2% cases of individuals with a constitutional trisomy 21. Low hypodiploidy, associated with a high risk of relapse, is rare in pediatric ALL cases in the general population, and, to our knowledge, is previously unreported in patients with trisomy 21.
Asunto(s)
Linfoma de Burkitt/genética , Diploidia , Síndrome de Down/genética , Linfoma de Burkitt/complicaciones , Preescolar , Síndrome de Down/complicaciones , Femenino , Humanos , Cariotipificación , MasculinoRESUMEN
Partial monosomy of the q2 region of chromosome 15 has been infrequently reported. Moreover, interstitial deletions involving 15q22-q24 have been described in only nine patients to date. The phenotype of these reported individuals is subject to the extent of the deletion but typically includes altered muscle tone and significant developmental delays. In addition, eye abnormalities, such as strabismus, microphthalmia, or colobomas, ear abnormalities including cleft earlobe and preauricular tags, and urogenital defects are common features. Congenital heart defects, diaphragmatic hernia, abnormalities of the central nervous system, and skeletal anomalies have been reported but appear to be less frequent clinical manifestations. In this report, we describe three new patients with interstitial deletions involving 15q24, two with cryptic deletions identified by fluorescence in situ hybridization (FISH) with a probe for the PML gene and one with a cytogenetically visible deletion of 15q22.3-q24. The clinical presentation of these individuals is similar to those previously described and includes global developmental delays, hypotonia, and genital abnormalities in the males. The identification of these three cases demonstrates that the above clinical features are associated with a new cytogenetic deletion syndrome. Furthermore, we suggest that FISH analysis with a probe for the PML gene be performed in patients with these physical findings.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 15/genética , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Niño , Bandeo Cromosómico , Sondas de ADN/genética , Discapacidades del Desarrollo/patología , Femenino , Genitales Masculinos/anomalías , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Cariotipificación , Masculino , Hipotonía Muscular/patología , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteína de la Leucemia Promielocítica , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
We describe a novel t(16;18)(p13;q21.3) in a male patient with follicular lymphoma. This unique chromosomal rearrangement has never been described in patients with follicular lymphoma. The breakpoint of 16p13 has several hematopoietic neoplasm-related genes such as MHC2TA, a master regulatory gene for HLA-D, and BCMA, tumor necrosis factor receptor super-family. The majority of follicular lymphomas have a rearrangement of the BCL2 gene, which is a pathogenetic factor in their development. The diagnostic and prognostic significance of this new translocation is yet to be determined.
Asunto(s)
Cromosomas Humanos Par 16 , Cromosomas Humanos Par 18 , Linfoma Folicular/genética , Translocación Genética , Genes bcl-2 , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A newborn female infant with multiple congenital anomalies was found to have an unusual and abnormal karyotype. Cytogenetic studies revealed an apparent balanced translocation between chromosome 4q31.3 and chromosome 6q25.1. Additional material on chromosome 2p was identified and determined to be from chromosome 6q by analysis with fluorescence in situ hybridization (FISH). The karyotype is 46,XX,der(2)t(2;6)(p23;q25.1), t(4;6)(q31.3;q25.1). Her mother has a normal female karyotype. The father was unavailable for physical examination or cytogenetic analysis.
Asunto(s)
Aberraciones Cromosómicas , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Cromosomas Humanos Par 2 , Cromosomas Humanos Par 4 , Cromosomas Humanos Par 6 , Diagnóstico Diferencial , Femenino , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Translocación GenéticaRESUMEN
This is a report of a trisomy 18 patient who developed Wilms tumor in conjunction with perilobar nephroblastomatosis (NB) at 9 years and 5 months of age. Review of the literature revealed that most patients with trisomy 18 who develop Wilms tumor, do so at a later than expected age for a tumor related to NB, and are females. In this case, no chromosome 11 WT1 mutation was detected by PCR/SSCP analysis, but the tumor had in addition to the trisomy, an isochromosome 7q and loss of heterozygosity at 16q, two mutations that have been linked independently to Wilms tumorigenesis.
Asunto(s)
Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 7/genética , Isocromosomas/genética , Neoplasias Renales/genética , Trisomía/genética , Tumor de Wilms/genética , Niño , Femenino , Humanos , Neoplasias Renales/patología , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Tumor de Wilms/patologíaAsunto(s)
Cromosomas Humanos Par 11/genética , Síndrome de Down/complicaciones , Leucemia Mieloide/diagnóstico , Mosaicismo/genética , Recurrencia Local de Neoplasia/diagnóstico , Trisomía/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Preescolar , Síndrome de Down/genética , Humanos , Cariotipificación , Leucemia Mieloide/complicaciones , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/genética , Leucemia Mieloide/patología , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patologíaRESUMEN
We have identified a constitutional inversion in chromosome 5 associated with familial adenomatous polyposis in three generations of a Mexican family. Two of three siblings developed hepatic neoplasia in infancy. The gene truncation assay failed to demonstrate a truncated protein in the segment harboring the adenomatous polyposis coli (APC) genes. Polymerase chain reaction (PCR) amplification of APC gene coding exons and sequencing of PCR products did not reveal any significant mutation. The data suggest that in this family, the phenotype may be the result of a "position effect."