Mosaic double aneuploidy: Down syndrome and XYY.

Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5‑year‑old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.

Discerning non-disjunction in down syndrome patients by means of GluK1-(AGAT) n and D21S2055-(GATA) n microsatellites on chromosome 21.

Introduction: Down syndrome (DS), the leading genetic cause of mental retardation, stems from non-disjunction of chromosome 21. Aim: Our aim was to discern non-disjunction in DS patients by genotyping GluK1-(AGAT) n and D21S2055-(GATA) n microsatellites on chromosome 21 using a family-based study design. Materials and Methods: We have used a PCR and automated DNA sequencing followed by appropriate statistical analysis of genotype data for the present study Results and Discussion: We show that a high power of discrimination and a low probability of matching indicate that both markers may be used to distinguish between two unrelated individuals. That the D21S2055-(GATA) n allele distribution is evenly balanced, is indicated by a high power of exclusion [PE=0.280]. The estimated values of observed heterozygosity and polymorphism information content reveal that relative to GluK1-(AGAT) n [H obs =0.286], the D21S2055- (GATA) n [H obs =0.791] marker, is more informative. Though allele frequencies for both polymorphisms do not conform to Hardy-Weinberg equilibrium proportions, we were able to discern the parental origin of non-disjunction and also garnered evidence for triallelic (1:1:1) inheritance. The estimated proportion of meiosis-I to meiosis-II errors is 2:1 in maternal and 4:1 in paternal cases for GluK1-(AGAT) n , whereas for D21S2055-(GATA) n , the ratio is 2:1 in both maternal and paternal cases. Results underscore a need to systematically evaluate additional chromosome 21-specific markers in the context of non-disjunction DS.

Estudio genómico de la región crítica del cromosoma 21 asociada con el síndrome de Down / Genomic study of the critical region of chromosome 21 associated to Down syndrome

Introduction: Previous reports have identified a region of chromosome 21 known as Down syndrome critical region (DSCR) in which the expression of some genes would modulate the main clinical characteristics of this pathology. In this sense, there is currently limited information on the architecture of the DSCR associated. Objective: To obtain in silico a detailed vision of the chromatin structure associated with the evaluation of genomic covariables contained in public data bases. Methods: Taking as reference the information consigned in the National Center for Biotechnology Information, the Genome Browser from the University of California at Santa Cruz and from the HapMap project, a chromosome walk along 21 Mb of the distal portion of chromosome 21q arm was performed. In this distal portion, the number of single nucleotide polymorphisms (SNP), number of CpG islands, repetitive elements, recombination frequencies, and topographical state of that chromatin were recorded. Results: The frequency of CpG islands and Ref genes increased in the more distal 1.2 Mb DSCR that contrast with those localized near to the centromere. The highest level of recombination calculated for women was registered in the 21q22.12 to 22.3 bands. DSCR 6 and 9 genes showed a high percentage of methylation in CpG islands in DNA from normal and trisomic fibroblasts. The DSCR2 gene exhibited high levels of open chromatin and also methylation in some lysine residues of the histone H3 as relevant characteristics. Conclusion: The existence of a genomic environment characterized by high values of recombination frequencies and CpG methylation in DSCR 6 and 9 and also DSCR2 genes led us to postulate that in non-disjunction detected in Down syndrome, complex genomic, epigenetic and environmental relationships regulate some processes of meiosis.

Introducción: Análisis previos han identificado una región del cromosoma 21, conocida como región crítica del síndrome de Down (DSCR) en donde se localizan algunos genes cuya expresión modularía las principales características clínicas de este síndrome. En este sentido, existe poca información detallada sobre la arquitectura de la cromatina asociada con la DSCR. Objetivo: Obtener in silico, a partir de la evaluación de covariables genómicas contenidas en bases de datos públicas, una visión detallada de la estructura cromatina asociada con la DSCR. Métodos: Tomando como referencia la información consignada en el National Center for Biotechnology Information, el Genome Browser de la Universidad de California en Santa Clara y el proyecto internacional HapMap, se efectuó un paseo cromosómico a lo largo de 21Mb de la porción distal del brazo q del cromosoma 21, para registrar el número de polimorfismos de nucleótido único, el de islas CpG, de secuencias repetidas, las tasas de recombinación y el estado topológico de la cromatina asociada. Resultados: La frecuencia de islas CpG y de genes referenciados se incrementó en los últimos 1,2 Mb de la región distal en contraste con su distribución pericentromérica. La mayor tasa de recombinación calculada en este estudio para mujeres se registró en las bandas 21q22.13 y 21q22.3. Los genes DSCR 6 y 9 presentaron un elevado grado de metilación en islas CpG tanto en fibroblastos normales como en trisómicos. En el gen DSCR2 se observó un alto grado de descondensación cromatínica, además de metilación de diferentes residuos de lisina de la histona H3. Conclusiones: La existencia de un ambiente genómico caracterizado por tener elevadas tasas de recombinación y de metilación de genes DSCR 6 y 9, permite postular que en la no disyunción asociada con el SD, operarían complejas interacciones genómicas, epigenéticas y ambientales que actuarían en algunos procesos meióticos.