RESUMO
Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk. Here we report genomic variations that in concert with trisomy 21, determine the risk for CHD in DS. This case-control GWAS includes 187 DS with CHD (AVSD = 69, ASD = 53, VSD = 65) as cases, and 151 DS without CHD as controls. Chromosome 21-specific association studies revealed rs2832616 and rs1943950 as CHD risk alleles (adjusted genotypic P-values <0.05). These signals were confirmed in a replication cohort of 92 DS-CHD cases and 80 DS-without CHD (nominal P-value 0.0022). Furthermore, CNV analyses using a customized chromosome 21 aCGH of 135K probes in 55 DS-AVSD and 53 DS-without CHD revealed three CNV regions associated with AVSD risk (FDR ≤ 0.05). Two of these regions that are located within the previously identified CHD region on chromosome 21 were further confirmed in a replication study of 49 DS-AVSD and 45 DS- without CHD (FDR ≤ 0.05). One of these CNVs maps near the RIPK4 gene, and the second includes the ZBTB21 (previously ZNF295) gene, highlighting the potential role of these genes in the pathogenesis of CHD in DS. We propose that the genetic architecture of the CHD risk of DS is complex and includes trisomy 21, and SNP and CNV variations in chromosome 21. In addition, a yet-unidentified genetic variation in the rest of the genome may contribute to this complex genetic architecture.
Assuntos
Variações do Número de Cópias de DNA , Síndrome de Down/diagnóstico , Cardiopatias Congênitas/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Cromossomos Humanos Par 21/genética , Proteínas de Ligação a DNA/genética , Síndrome de Down/complicações , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Cardiopatias Congênitas/etiologia , Humanos , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Fatores de Transcrição/genéticaRESUMO
The use of new technology seems to be an important factor that contributes to the overall ability to adapt and achieve higher independence. Technologies using digital games have gained the great interest of the scientific community as there are many advantages for both effectiveness and benefits, physically and mentally, providing the opportunity for essential and enjoyable training. This study presents an important initial step utilizing the LLM Care service which focuses on the needs and challenges for the health and daily living of people with Down syndrome (DS) by applying new technology hardware and software. People with cognitive impairments, such as memory, attention and motivation problems may also benefit from this kind of cognitive support that assistive technology offers.