RESUMEN
BACKGROUND: Down syndrome (DS) is the most common chromosomal survival aneuploidy. The increase in DS life expectancy further heightens the risk of dementia, principally early-onset Alzheimer's disease (AD). AD risk in DS is higher, considering that this population may also develop metabolic diseases such as obesity, dyslipidemias, and diabetes mellitus. The extra genetic material that characterizes DS causes an imbalance in the genetic dosage, including over-expression of AD's key pathophysiological molecules and the gene expression regulators, the microRNAs (miRNAs). Two miRNAs, chromosome 21-encoded, miR-155, and let-7c, are associated with cognitive impairment and dementia in adults; but, expression dynamics and relationship with clinical variables during the DS's lifespan had remained hitherto unexplored. METHODS: The anthropometric, clinical, biochemical, and profile expression of circulating miR-155 and let-7c were analyzed in a population of 52 control and 50 DS subjects divided into the young group (Aged ≤20 years) and the adult group (Aged ≥21 years). RESULTS: The expression changes for miR-155 were not significant; nevertheless, a negative correlation with HDL-Cholesterol concentrations was observed. Notably, let-7c was over-expressed in DS from young and old ages. CONCLUSION: Overall, our results suggest that let-7c plays a role from the early stages of DS's cognitive impairment while overexpression of miR-155 may be related to lipid metabolism changes. Further studies of both miRNAs will shed light on their potential as therapeutic targets to prevent or delay DS's cognitive impairment.
Asunto(s)
Enfermedad de Alzheimer , MicroARN Circulante , Síndrome de Down , MicroARNs , Adulto , Enfermedad de Alzheimer/genética , Cromosomas Humanos Par 21/genética , Síndrome de Down/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
Intrachromosomal amplification of chromosome 21 (iAMP21) occurs in â¼2% of B-cell acute lymphoblastic leukemia (ALL) and is considered to confer a poor prognosis. The relapse risk is associated with therapy intensity, suggesting that other somatic mutations may influence iAMP21-ALL prognosis. This abnormality is characterized by multiple copies of the RUNX1 gene in chromosome 21 and appears to arise through multiple breakage-fusion bridge cycles and chromothripsis. Rob(15;21) or a ring chromosome 21 have been associated with an increased risk for iAMP21-ALL, suggesting that constitutional genetic abnormalities may also drive leukemogenesis. Here we describe homozygous deletion of the SH2B3 gene, chromothripsis of chromosome 21, and a non-Robertsonian somatic t(15;21)(q25.3;q22.1) with NTRK3 gene rearrangement in an adolescent with iAMP21-B-ALL. Molecular cytogenetic studies detected iAMP21 with aCGH analysis revealing further genomic imbalances. The RT-qPCR analysis detected elevated expression levels of RUNX1 (68-fold) and reduced expression of CDK6 (0.057-fold). Studies with constitutive cells collected from mouth swabs showed that SH2B3 biallelic deletion was a somatic alteration occurring during clonal evolution. The identification of novel secondary genetic changes was valuable to discuss sporadic iAMP21 leukemogenic mechanisms. For the first time, we show a t(15;21)(q25.3;q22.1) with NTRK3 rearrangement in an adolescent with iAMP21-ALL.
Asunto(s)
Linfoma de Burkitt , Cromotripsis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Cromosomas en Anillo , Adolescente , Linfoma de Burkitt/genética , Cromosomas Humanos Par 21/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Homocigoto , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Células Precursoras de Linfocitos B , Eliminación de Secuencia , Translocación GenéticaRESUMEN
Monosomy 21 is an exceedingly rare and fatal chromosomal anomaly. Mosaic monosomy 21, however, can be observed in living patients. There have been discussions on whether there are liveborn cases with true mosaic full monosomy 21. Here, we report the case of a 13-year-old patient with mosaic full monosomy 21 who presented with postnatal microcephaly, low weight, facial dysmorphisms, developmental delay, and severe intellectual disability. To the best of our knowledge, this is the oldest patient with mosaic full monosomy 21 described so far and the first reported in Brazil.
Asunto(s)
Trastornos de los Cromosomas , Discapacidad Intelectual , Adolescente , Brasil , Cromosomas Humanos Par 21 , Femenino , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Monosomía/genéticaRESUMEN
Adults with Down syndrome are at high risk for Alzheimer's disease (AD), with most individuals developing clinical dementia by their late 60s. This increased risk for AD has been attributed, at least in part, to triplication and overexpression of the gene for amyloid precursor protein (APP) on chromosome 21, leading to elevated levels of amyloid ß peptides. This article offers a brief overview of our current knowledge of AD in the DS population. In addition, information on a NIA/NICHD-funded, multicenter longitudinal study of biomarkers of AD in adults with DS is provided.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Precursor de Proteína beta-Amiloide/metabolismo , Biomarcadores , Síndrome de Down/diagnóstico , Neuroimagen , Pruebas Neuropsicológicas , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Precursor de Proteína beta-Amiloide/genética , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Cromosomas Humanos Par 21/genética , Comorbilidad , Síndrome de Down/epidemiología , Síndrome de Down/metabolismo , Síndrome de Down/fisiopatología , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , National Institutes of Health (U.S.) , Riesgo , Estados UnidosRESUMEN
Orofacial clefts (OFCs) are among the most prevalent craniofacial birth defects worldwide and create a significant public health burden. The majority of OFCs are non-syndromic, and the genetic etiology of non-syndromic OFCs is only partially determined. Here, we analyze whole genome sequence (WGS) data for association with risk of OFCs in European and Colombian families selected from a multicenter family-based OFC study. This is the first large-scale WGS study of OFC in parent-offspring trios, and a part of the Gabriella Miller Kids First Pediatric Research Program created for the study of childhood cancers and structural birth defects. WGS provides deeper and more specific genetic data than using imputation on present-day single nucleotide polymorphic (SNP) marker panels. Genotypes of case-parent trios at single nucleotide variants (SNV) and short insertions and deletions (indels) spanning the entire genome were called from their sequences using human GRCh38 genome assembly, and analyzed for association using the transmission disequilibrium test. Among genome-wide significant associations, we identified a new locus on chromosome 21 in Colombian families, not previously observed in other larger OFC samples of Latin American ancestry. This locus is situated within a region known to be expressed during craniofacial development. Based on deeper investigation of this locus, we concluded that it contributed risk for OFCs exclusively in the Colombians. This study reinforces the ancestry differences seen in the genetic etiology of OFCs, and underscores the need for larger samples when studying for OFCs and other birth defects in populations with diverse ancestry.
Asunto(s)
Cromosomas Humanos Par 21/genética , Labio Leporino/genética , Fisura del Paladar/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Secuenciación Completa del Genoma/métodos , Niño , Colombia , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , MasculinoRESUMEN
El síndrome de Down es causado por la presencia de una tercera copia del cromosoma 21 y fue descrito por primera vez en 1838 por Jean-Etienne-Dominique, y más tarde por John Langdon Haydon Down en 1866, mientras trabajaba como superintendente médico en el Asilo Real de Earlswood. Desde ese momento, la comunidad científica puso grandes esfuerzos en tratar de elucidar diversos aspectos que influyen en la naturaleza de esta condición, y que determinan su incidencia y factores de riesgo. De igual manera, se ha puesto interés en los genes involucrados en esta enfermedad, la relación genotipo-fenotipo, la expresión del fenotipo, la variabilidad del material genético y las consecuencias transcripcionales que se producen al tener una tercera copia, ya sea parcial o total, del cromosoma 21. Además, se han invertido esfuerzos en identificar biomarcadores y en diseñar metodologías de diagnóstico prenatal no invasivo que sean altamente eficientes para un mejor diagnóstico del síndrome de Down, y así reducir su impacto negativo en las madres gestantes, al proveerlas de información neutral y precisa acerca de vivir con un hijo con síndrome de Down, y darles autonomía en la decisión de la continuación de su embarazo
Down syndrome is caused by the presence of a third copy of chromosome 21 and was first described by Jean-Etienne-Dominique in 1838, and later by John Langdon Haydon Down in 1866, while working as a medical superintendent in the Royal Earlswood Asylum. Since, the scientific community has placed great efforts in trying to elucidate different influencing features in the nature of this condition that determine their incidence and risk factors. In addition, especial attention has been given to the genes involved in this disease, the genotype-phenotype relationship, the expression of the phenotype, the variability of the genetic material and the transcriptional consequences that are produced by having a third copy, either partial or total, of chromosome 21. Additionally, efforts have been invested in identifying biomarkers and designing noninvasive prenatal methodologies that are highly efficient for a better diagnosis of Down syndrome, in order to reduce its negative impact in pregnant mothers, by providing them with neutral and accurate information about life with a child with Down syndrome, as well as providing the autonomy in the decision to continue their pregnancy
Asunto(s)
Cromosomas Humanos Par 21 , Fenotipo , Síndrome de Down , Ácidos Nucleicos Libres de CélulasAsunto(s)
Síndrome de Down/genética , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , California/epidemiología , California/etnología , Estudios de Casos y Controles , Niño , Preescolar , Cromosomas Humanos Par 21/genética , Síndrome de Down/complicaciones , Síndrome de Down/etnología , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Guatemala/epidemiología , Guatemala/etnología , Haplotipos , Hispánicos o Latinos , Humanos , Lactante , Recién Nacido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnología , Análisis de Componente Principal , Factores de Riesgo , Regulador Transcripcional ERG/genéticaRESUMEN
Recent investigations have shown that isochores are characterized by a 3-D structure which is primarily responsible for the topology of chromatin domains. More precisely, an analysis of human chromosome 21 demonstrated that low-heterogeneity, GC-poor isochores are characterized by the presence of oligo-Adenines that are intrinsically stiff, curved and unfavorable for nucleosome binding. This leads to a structure of the corresponding chromatin domains, the Lamina Associated Domains, or LADs, which is well suited for interaction with the lamina. In contrast, the high-heterogeneity GC-rich isochores are in the form of compositional peaks and valleys characterized by increasing gradients of oligo-Guanines in the peaks and oligo-Adenines in the valleys that lead to increasing nucleosome depletions in the corresponding chromatin domains, the Topological Associating Domains, or TADs. These results encouraged us to investigate in detail the di- and tri-nucleotide profiles of 100 Kb segments of chromosome 21, as well as those of the di- to octa-Adenines and di- to octa-Guanines in some representative regions of the chromosome. The results obtained show that the 3-D structures of isochores and chromatin domains depend not only upon oligo-Adenines and oligo-Guanines but also, to a lower but definite extent, upon the majority of di- and tri-nucleotides. This conclusion has strong implications for the biological role of non-coding sequences.
Asunto(s)
Cromosomas Humanos Par 21/química , Genoma Humano , Isocoras/química , Isocoras/síntesis química , Nucleosomas/química , HumanosAsunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 21/química , Discapacidad Intelectual/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas Serina-Treonina Quinasas/genética , Proteína-Arginina N-Metiltransferasas/genética , Adulto , Femenino , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/fisiopatología , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Cariotipificación , Fenotipo , Proteínas Serina-Treonina Quinasas/deficiencia , Proteína-Arginina N-Metiltransferasas/deficienciaRESUMEN
Partial monosomy 21 results in a great variability of clinical features that may be associated with the size and location of the deletion. In this study, we report a 22-month-old girl who showed a 45,XX,add(12)(p13)dn,-21 karyotype. The final cytogenomic result was 45,XX,der(12)t(12;21)(p13;q22.11) dn,-21.arr[hg19] 21q11.2q22.11(14824453_33868129)×1 revealing a deletion from 21pter to 21q22.11. Clinical manifestation of the patient included hypertonia, a long philtrum, epicanthic folds, low-set ears, and café-au-lait macules - a phenotype considered as mild despite the relatively large size of the deletion compared to patients from the literature.
Asunto(s)
Anomalías Múltiples/genética , Manchas Café con Leche/genética , Deleción Cromosómica , Cromosomas Humanos Par 21/ultraestructura , Cara/anomalías , Hipertonía Muscular/genética , Cromosomas Humanos Par 21/genética , Discapacidades del Desarrollo/genética , Femenino , Pérdida Auditiva Bilateral/genética , Humanos , Recién Nacido , Cariotipificación , Fenotipo , Escoliosis/genéticaRESUMEN
A leucemia linfoblástica aguda de células precursoras B (LLA-CPB) é uma neoplasia heterogênea. Aproximadamente 60% das LLA-CPB apresentam alterações envolvendo o cromossomo 21, incluindo hiperdiploidia, fusão gênica ETV6‐UNX1 e amplificação intracromossomal do cromossomo 21 (iAMP21). Mecanismos epigenéticos contribuem para a leucemogênese e a metilação do DNA, por sua vez, pode ser modulada por polimorfismos na via do folato. Portanto, este estudo tem como objetivo caracterizar o perfil genético e de metilação de DNA em LLA-CPB com alterações no cromossomo 21. Este estudo partiu de uma série de 1006 casos de LLA-CPB diagnosticados de 2002-2016 e foi desenhado em 3fases: 1) Identificação dos casos com alterações em número de cópias (CNA) no cromossomo 21 usando multiplex ligation probe amplification (MLPA) e FISH (RUNX1 e sondas para os cromossomos 4, 8, 10, 14, 17, 18, X e Y); 2) Caracterização do perfil de metilação e CNA por meio da técnica de microarranjo. Para tanto, o DNA foi modificado com EZ DNA Methylation Kit e o perfil de metilação analisado pelo Infinium Human Methylation 450 BeadChip Kit; e 3) Análises comparativas de metilação de DNA gene-específica, metilação em LINE-1(pirosequenciamento) e genotipagem para o polimorfismo MTHFR rs1801133 (PCR-RFLP) entre os diferentes subtipos moleculares de LLA-CPB, controles e amostras em remissão. Encontramos evidências de ganhos em CNA no cromossomo 21 em 83/374 (22%) das amostras (MLPA)...
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous disease. Approximately 60% of BCP-ALL present alterations involving chromosome 21 (chr 21), including high hyperdiploid, ETV6‐RUNX1 fusion and intrachromosomal amplification of thechromosome 21 (iAMP21). Contributing with this process, epigenetic mechanisms could regulate the transcription and induce leukemogenesis. Polymorphisms in genes involved in folate metabolism could influence this aberrant methylation. This study aimed to characterize the genetic and DNA methylation profile of BCP-ALL with chr 21 aberrations, as well as to identify the DNA methylation signatures of different BCP-ALL molecular subgroups. This study enrolled 1006 BCP-ALL diagnosed between 2002-2016 and was performed in tree steps: 1) Identification of copy number alterations (CNA) regarding the Chr 21 by multiplex ligation probe amplification (MLPA) and FISH (LPH012 TEL/AML1 translocation, dual fusion probe and centromere probes to chr 4, 8, 10, 14, 17, 18, X and Y); 2) DNA methylation and CNAcharacterization by DNA methylation array. DNA from BCP-ALL cases, controls and remission samples was modified with EZ DNA Methylation Kit and analyzed by the InfiniumHumanMethylation450 BeadChip Kit; 3) Comparative gene methylation, LINE-1 methylation (pyrosequencing) and MTHFR rs1801133 genotype (PCR-RFLP) analysis between the different BCP-ALL subgroups. We found evidence of gains in chr 21 in 83/374 (22%) of the samples analyzed by MLPA. Among the BCP-ALL with chr 21 gains, 11/83 (13%) had ≥5 RUNX1 signals and 53/83 (64%) were classified as hyperdiploid...
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Cromosomas Humanos Par 21/genética , Leucemia Bifenotípica Aguda , Metilación de ADNRESUMEN
Introducción: la monosomía del cromosoma 21, generalmente es incompatible con la vida, aunque se reportan casos en los que esta aparece en forma de mosaico, y constituye un hallazgo inusual en los estudios genéticos realizados en Pediatría.Presentación del caso: niña de 7 años de edad, que fue remitida a la consulta de Asesoramiento Genético por presentar malformaciones congénitas severas y rasgos dismórficos, asociado a un retardo del neurodesarrollo. Al nacer se diagnosticó una comunicación interauricular, que requirió cirugía. Se le realizó estudio por técnicas de citogenética convencional y se obtuvo como resultado una inusual monosomía del cromosoma 21. El estudio de técnica de citogenética molecular detectó una inserción de la zona crítica del 21 en la región subtelomérica del 6p.Conclusiones: el correcto examen clínico de la paciente, unido a los métodos moleculares empleados, permite establecer una hipótesis del diagnóstico de este caso tan inusual(AU)
Asunto(s)
Humanos , Femenino , Niño , Monosomía/genética , Cromosomas Humanos Par 21/genética , Análisis Citogenético/métodos , Diagnóstico Clínico/diagnósticoRESUMEN
Quantitative fluorescent polymerase chain reaction (QF-PCR), in recent years, has been accepted as a rapid, high throughput, and sensitive method for prenatal diagnosis of common chromosomal aneuploidies. Since short tandem repeats (STRs) are the cornerstone of QF-PCR technique, selection of the most polymorphic STR markers is an essential step for a successful QF-PCR assay. The genetic variation parameters of each STR marker differ among different populations. In this study, we investigated the size, frequency, heterozygosity, polymorphism information content, power of discrimination, and other genetic polymorphism data for 21 STR markers on chromosomes 13, 18, 21, X, and Y in 1000 amniotic fluid samples obtained from south Iranian women. Our results showed that all the 21 STR markers are highly polymorphic and informative in our population. The heterozygosity, polymorphism information content, and power of discrimination of the markers were 62-91.1%, 0.61-0.91, and 0.830-0.976, respectively. The locus D18S386 was the most polymorphic STR, while the locus DXYS218 was the least polymorphic STR among all the studied STRs. The present study has provided extensive data regarding the efficiency of the 21 STR markers for diagnosis of chromosomes 13, 18, 21, X, and Y aneuploidies in the south Iranian population.
Asunto(s)
Cromosomas Humanos/genética , Repeticiones de Microsatélite , Diagnóstico Prenatal/métodos , Población Blanca/genética , Líquido Amniótico/química , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 21/genética , Cromosomas Humanos X/genética , Cromosomas Humanos Y/genética , Femenino , Frecuencia de los Genes , Variación Genética , Humanos , Irán , Masculino , EmbarazoRESUMEN
BACKGROUND: Genetic disorders are a major cause in the etiology of cases with intellectual disability; however, analysis by a conventional technique such as cytogenetic karyotyping only allows the detection of chromosomal alterations in approximately 9.5 % of cases. The inclusion of new technologies such as high resolution microarray analysis has allowed the study of alterations in chromosomal segments that are less than 5 Mb in length; this has led to an increase in the diagnosis of these patients of up to 25 %. CASE PRESENTATION: We report the first case of an 8-year-old Colombian girl of mixed race ancestry (Mestizo), with clinical features that include: delayed psychomotor and language development, intellectual disability, upward slanting palpebral fissures, divergent strabismus, low-set and rotated ears, tall and broad nasal bridge, flat philtrum, bifid uvula, posterior cleft palate, increased anteroposterior diameter of her chest, congenital heart defect type interventricular communication, scoliosis, and umbilical hernia. Genetic analysis was performed using comparative genomic hybridization array, which evidenced the deletion of a region of approximately 3.608 Mb on chromosome 21q22.3, and a duplication of 12.326 Mb on chromosome 7q35q36.3, these alterations affect approximately 112 and 186 genes, respectively. CONCLUSIONS: To date, this is the first report of an associated terminal deletion of 21q and 7q duplication in a patient with delayed psychomotor development and intellectual disability. We consider that future implementation of exome and RNA sequencing techniques, and analysis of their proteomic expression in a clinical context could lead to better analysis and interpretation of the genotype-phenotype correlation in cases similar to that described.
Asunto(s)
Anomalías Múltiples/genética , Discapacidades del Desarrollo/genética , Trisomía/diagnóstico , Trisomía/genética , Anomalías Múltiples/diagnóstico , Niño , Deleción Cromosómica , Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 7/genética , Colombia , Hibridación Genómica Comparativa/métodos , Discapacidades del Desarrollo/complicaciones , Diagnóstico Diferencial , Femenino , Estudios de Asociación Genética/métodos , Humanos , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/genética , Análisis por Micromatrices/métodos , Proteómica/métodosRESUMEN
In addition to previously studied immunological variables, the relative expression of IFNGR2, IFNAR1, CD18, and CD275 (all encoded in chromosome 21) on circulating leucocytes and multifunctional T cells (evaluated by an intracellular cytokine/proliferation assay) were compared between children with Down syndrome (DS) and healthy controls (HC). As previously reported, numbers of lymphocytes, CD4(+) T cells, Treg cells, B cells, and levels of serum IgM were decreased, and levels of IgG and IgA were increased in children with DS. Moreover, the relative expression of CD18 on T and B cells (previously and not previously reported, respectively) were elevated in DS children (p⩽0.01). Age and numbers of B and Treg cells moderately correlated with retrospectively identified infection related hospitalizations (rho: 0.300-0.460, p⩽0.003). Age and the numbers of Treg cells also correlated with prospectively identified infection related hospitalizations. Future studies are necessary to clarify the role of these parameters in the immunity of DS patients.
Asunto(s)
Linfocitos B/inmunología , Cromosomas Humanos Par 21/genética , Síndrome de Down/inmunología , Hospitalización/estadística & datos numéricos , Infecciones/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Antígenos CD18/metabolismo , Proliferación Celular , Niño , Preescolar , Citocinas/metabolismo , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Femenino , Humanos , Ligando Coestimulador de Linfocitos T Inducibles/metabolismo , Lactante , Infecciones/complicaciones , Infecciones/epidemiología , Activación de Linfocitos , Masculino , Receptor de Interferón alfa y beta/genética , Receptor de Interferón alfa y beta/metabolismo , Receptores de Interferón/genética , Receptores de Interferón/metabolismoRESUMEN
Se presenta el caso de una niña de 7 años de edad, que fue remitida a la Consulta de Asesoramiento Genético, por presentar malformaciones congénitas severas y rasgos dismórficos, asociado a un retardo del neurodesarrollo. Al nacer se diagnosticó una comunicación interauricular, lo cual fue corregido mediante operación cardiaca. Se le realizó estudio por técnicas de citogenética convencional obteniéndose como resultado una monosomía del cromosoma 21. El estudio de citogenética molecular por técnica FISH detectó una inserción de la zona crítica del 21 en la región subtelomérica del 6p.
The case of a 7-year-old girl is showed. She was referral to the Genetic Advice Session, for presenting severe congenital malformations and dysmorphisms, associated with a neurological delay. A canal inter auricle was diagnosed at birth, which was corrected through heart surgery. The conventional cytogenetic analyzed showed a 21 chromosome monosomy. The study of molecular cytogenetic detected an insertion of the critical region of 21 in the subteloméric 6p region.
Asunto(s)
Humanos , Femenino , Niño , Cromosomas Humanos Par 21/genética , Monosomía/diagnóstico , Monosomía/genética , Enfermedades del Sistema Nervioso , Anomalías Congénitas , Deleción Cromosómica , Análisis CitogenéticoRESUMEN
A reciprocal translocation between the short arm of chromosome 1 and the long arm of chromosome 3 was observed in a pedigree of three carriers (proband, and his brother and mother). In this study, the three carriers had different clinical manifestations: the proband with infertility, his brother with spousal miscarriages, and his mother with no adverse reproductive history. Cytogenetic analysis of metaphase chromosomes was performed, and triple-color fluorescence in situ hybridization was applied to the detection of aneuploidy sperm related to the interchromosomal effect (ICE). An increase of aneuploidy of chromosome 21 in the proband and aneuploidy of chromosomes 13, 21, and Y in the brother were observed. Since patients with reciprocal translocations and spermatogenetic impairment are candidates, with their partners, for intracytoplasmic sperm injection, the study of the level of sperm aneuploidy rates would provide useful information for couples at risk, as well as contributing to a better understanding of the ICE.
Asunto(s)
Aneuploidia , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 3 , Infertilidad Masculina/genética , Espermatozoides/metabolismo , Translocación Genética , Adulto , Cromosomas Humanos Par 13 , Cromosomas Humanos Par 21 , Cromosomas Humanos Y , Análisis Citogenético , Femenino , Asesoramiento Genético , Heterocigoto , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Linaje , Espermatozoides/patologíaRESUMEN
Short tandem repeats (STRs) are highly polymorphic sequences and have been extensively used as genetic markers in mapping studies, disease diagnosis, and human identity testing. In this study, 11 STR markers on chromosome 21, including D21S1432, D21S11, D21S1246, D21S1412, D21S1437, D21S1442, D21S2039, D21S1270, D21S1435, D21S1409, and D21S1446, were analyzed in 740 unrelated Han individuals from southeast China. A total of 132 alleles, ranging from 7-21 for each locus, were named according to the guidelines of the International Society for Forensic Haemogenetics. The distributions of allelic frequencies for the 11 STRs and population genetic parameters were determined. All 11 STR markers showed high polymorphism and heterogeneity in the southeast Han population, with polymorphism information content of 0.61-0.87, heterogeneity of 64.5-86.1%, and power of discrimination of 0.835-0.973. Among the 11 STR markers, D21S1412, D21S1270, D21S11, and D21S1442 showed relatively higher heterogeneity. Their combination was relatively informative and was used in a quantitative fluorescence-polymerase chain reaction assay to diagnose Down syndrome (trisomy 21) in a southeast Chinese Han population. The genetic information and population data for these 11 STRs may be used not only in quantitative fluorescence-polymerase chain reaction assays but also in forensic studies and other genetic tests.
Asunto(s)
Cromosomas Humanos Par 21/genética , Marcadores Genéticos , Repeticiones de Microsatélite , Alelos , Pueblo Asiatico/genética , China , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Frecuencia de los Genes , Pruebas Genéticas , Humanos , Filogeografía , Polimorfismo GenéticoRESUMEN
INTRODUCCIÓN: la enfermedad de Alzheimer (EA) es una enfermedad neurodegenerativa de evolución progresiva que representa el tipo más común de demencia. El riesgo de presentar enfermedad de Alzheimer familiar (EAF) puede aumentar 2 a 4 veces entre los individuos que tienen un familiar de primer grado con la enfermedad, para la cual se han identificado mutaciones en tres genes, definidas como causales (PSEN-1, PSEN-2 y APP). OBJETIVO: evaluar la utilidad del estudio molecular de los genes PSEN-1, PPA, PSEN-2 (cromosomas 14, 21 y 1) en el diagnóstico de enfermedad de Alzheimer de inicio temprano (EAIT). METODOLOGÍA: se realizó una búsqueda de evidencia en las bases de datos: MEDLINE, EMBASE, la Librería Cochrane y LILACS. Dos evaluadores de manera independiente, tamizaron las referencias obtenidas, resolviendo las discrepancias por consenso. Se identificaron únicamente estudios descriptivos, a partir de los cuales se basan los resultados del presente informe. RESULTADOS: se identificaron 5 estudios descriptivos. Los estudios confirman la identificación de los 3 genes determinantes en la aparición de la enfermedad de EAIT; las mutaciones más frecuentemente identificadas son las pertenecientes al gen PSEN-1. CONCLUSIONES: el estudio molecular de los genes PSEN-1, PSEN-2 y PPA en pacientes con demencia de inicio temprano (< de 65 años) e historia familiar de demencia, se considera el patrón de oro para el diagnóstico de EAIT de transmisión autosómico dominante.(AU)
Asunto(s)
Humanos , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 21/genética , Enfermedad de Alzheimer/diagnóstico , Análisis Costo-Beneficio , Colombia , Enfermedad de Alzheimer/genéticaRESUMEN
Individuals with Down syndrome (DS) have a high incidence of immunological alterations with increased susceptibility to bacterial and viral infections and high frequency of different types of hematologic malignancies and autoimmune disorders. In the current study, we profiled the expression pattern of 92 immune-related genes in peripheral blood mononuclear cells (PBMCs) of two different groups, children with DS and control children, to identify differentially expressed genes that might be of pathogenetic importance for the development and phenotype of the immunological alterations observed in individuals with DS. PBMCs samples were obtained from six DS individuals with karyotypically confirmed full trisomy 21 and six healthy control individuals (ages 2-6 years). Gene expression was profiled in duplicate according to the manufacturer's instructions provided by commercially available TaqMan Human Immune Array representing 92 immune function genes and four reference genes on a 96-plex gene card. A set of 17 differentially expressed genes, not located on chromosome 21 (HSA21), involved in immune and inflammatory pathways was identified including 13 genes (BCL2, CCL3, CCR7, CD19, CD28, CD40, CD40LG, CD80, EDN1, IKBKB, IL6, NOS2 and SKI) significantly down-regulated and four genes (BCL2L1, CCR2, CCR5 and IL10) significantly up-regulated in children with DS. These findings highlight a list of candidate genes for further investigation into the molecular mechanism underlying DS pathology and reinforce the secondary effects of the presence of a third copy of HSA21.