Telomere length in inherited bone marrow failure syndromes

Twenty years of the Italian Fanconi Anemia Registry: where we stand and what remains to be learned

“…24 In our Registry, we have not systematically investigated any genotype-phenotype correlation; 25 however, genetic data from a subset of patients (as well as independent data on the genetics of FA in the same geographic area) 26 seem predominantly influenced by the large prevalence of patients harboring FANCA mutations. 21,27 Malignancies play an important role in the natural history of FA, the risk increasing with age for a wide array of cancer types; [10][11][12]18 moreover, some patients can develop multiple cancers, possibly also due to the increased risk associated with anti-cancer treatments (i.e., chemotherapy and radiotherapy). This report confirms the cancer propensity of FA patients and further stresses the need for frequent and careful tumor evaluations, aiming at early therapeutic interventions, 24,28 the only effective strategy for improving long-term survival in FA patients.…”

“…FA patients can show variable congenital malformations 9 and are prone to hematologic and solid neoplasias, which are ultimately the leading cause of death. 1,4,[10][11][12] At present, hematopoietic stem cell transplantation (HSCT) represents the only effective treatment for FA, 13 although unfortunately it cannot improve the patient's growth rate or reduce the propensity to develop non-hematological cancers.…”

The European Hematology Association Roadmap for European Hematology Research: a consensus document

“…Inherited BMFs include different entities, such as Fanconi anemia (FA) (which is due to impaired DNA repair and cytokine hypersensitivity), 172,173 dyskeratosis congenita, Diamond Blackfan anemia (DBA), and Shwachman-Diamond syndrome (all associated with impaired ribosomal or telomere function). Inherited BMFs are rare disorders, the most common of which is FA (1-3 per 500,000 newborns).…”

Marked overlap of four genetic syndromes with dyskeratosis congenita confounds clinical diagnosis

“…13,14,20,23,24 In the remaining families we have provided strong genetic and in silico evidence that the identified mutations are pathogenic. This study has demonstrated that the pleotropic clinical phenotype of DC markedly overlaps with the recognized disease entities LIG4 syndrome, Dubowitz syndrome and PN as well as the recently recognized ECTDS.…”

“…18,19 In fact, this measure is often used as a diagnostic screening tool to perform a differential diagnosis of DC from other bone marrow failure syndromes such as Fanconi anemia. 20 Telomere lengths were therefore measured in our patients by MMqPCR, and this was used as an indicator of whether we could be looking for a mutation in a known telomere biology related gene or not. As none of the patients reported in this study had short telomeres when compared with controls (Figure 1), this suggested that we were looking for mutations outside the spectrum of those usually associated with DC, but they could still be associated with other bone marrow failure diseases or else have a previously unidentified association to another pathology.…”