Česká Genetická Banka

BLOOD: 17. 7. 2014

BLOOD: Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist

"Most patients who require allogeneic stem cell transplantation do not have a matched sibling donor, and many patients do not have a matched unrelated donor. In an effort to increase the applicability of transplantation, alternative donors such as mismatched adult unrelated donors, haploidentical related donors, and umbilical cord blood stem cell products are frequently used when a well matched donor is unavailable. We do not yet have the benefit of randomized trials comparing alternative donor stem cell sources to inform the choice of donor; however, the existing data allow some inferences to be made on the basis of existing observational and phase 2 studies. All 3 alternative donor sources can provide effective lymphohematopoietic reconstitution, but time to engraftment, graft failure rate, graft-versus-host disease, transplant-related mortality, and relapse risk vary by donor source. These factors all contribute to survival outcomes and an understanding of them should help guide clinicians when choosing among alternative donor sources when a matched related or matched unrelated donor is not available."

http://www.bloodjournal.org/content/124/3/334

 

NATURE: Genome sequencing identifies major causes of severe intellectual disability

"Severe intellectual disability (ID) occurs in 0.5% of newborns and is thought to be largely genetic in origin1, 2. The extensive genetic heterogeneity of this disorder requires a genome-wide detection of all types of genetic variation. Microarray studies and, more recently, exome sequencing have demonstrated the importance of de novo copy number variations (CNVs) and single-nucleotide variations (SNVs) in ID, but the majority of cases remain undiagnosed3, 4, 5, 6. Here we applied whole-genome sequencing to 50 patients with severe ID and their unaffected parents. All patients included had not received a molecular diagnosis after extensive genetic prescreening, including microarray-based CNV studies and exome sequencing. Notwithstanding this prescreening, 84 de novo SNVs affecting the coding region were identified, which showed a statistically significant enrichment of loss-of-function mutations as well as an enrichment for genes previously implicated in ID-related disorders. In addition, we identified eight de novo CNVs, including single-exon and intra-exonic deletions, as well as interchromosomal duplications. These CNVs affected known ID genes more frequently than expected. On the basis of diagnostic interpretation of all de novo variants, a conclusive genetic diagnosis was reached in 20 patients. Together with one compound heterozygous CNV causing disease in a recessive mode, this results in a diagnostic yield of 42% in this extensively studied cohort, and 62% as a cumulative estimate in an unselected cohort. These results suggest that de novo SNVs and CNVs affecting the coding region are a major cause of severe ID. Genome sequencing can be applied as a single genetic test to reliably identify and characterize the comprehensive spectrum of genetic variation, providing a genetic diagnosis in the majority of patients with severe ID."