TINF2 (TERF1 Interacting Nuclear Factor 2)

These two patients presented with BMF, identified to have VUSs in more than one TBD-associated gene with functional evidence of shortened telomeres, highlighting the potential for a digenic mode of inheritance. Synergy between two VUSs could contribute to a penetrant phenotype and resulting in earlier or more severe onset of disease.

Our results underscore the need for disease-specific translational studies as well as improved prevention and therapeutic options for patients with TBDs. Trial Registration: ClinicalTrials.gov identifier: NCT00027274.

A novel AIP variant, and novel variations in syndromic genes were identified, along with the introduction of candidate genes. WES method is a crucial approach to identify new rare genetic variants in familial settings, and it will pave the way for future studies on targeted therapies.

Although dyskeratosis congenita is a rare disease, it can be indicated by simple examination. When patients, especially younger ones, present with typical skin changes, nail dysplasia and bone marrow failure due to interstitial pneumonia, respiratory specialists should maintain a high index of suspicion for this condition and perform relevant genetic testing early to confirm the diagnosis.

Cancer risks increased after organ transplant across all subgroups. These differences in TBD-associated cancer risks by mode of inheritance suggest cancer screening could be tailored by genotype, but additional research is warranted.

Insights into TPP1-associated glycans highlighted glycosylated sites contributing to tumorigenesis. This study provides molecular signatures for further functional and therapeutic research on shelterin, highlighting its potential as a target for anti-cancer therapies and promising prospects for cancer prognosis and prediction.

Our results reinforce the TINF2 gene as a susceptibility cause of FNMTC suggesting the importance of location of frameshift variants in TINF2. According to our data and previous literature, TINF2 pathogenic variants appear to be a significant risk factor for the development of NMTC and/or melanoma.

These data identify a syndromic subset of PTCs with locus heterogeneity and telomere lengthening as a convergent mechanism. They suggest these germline variants lower the threshold to cancer by obviating the need for an acquired telomere-maintenance mechanism in addition to sustaining the longevity of oncogenic mutations.

He then underwent reduced intensity conditioning using busulfan, fludarabine and anti-thymocyte globulin for a 4/6 matched cord stem cell transplant. Our patients' parents were asymptomatic or mildly affected, compared to our patients. Larger cohort studies are needed to determine the prevalence of this mode of inheritance.

In addition, only 9 out of 215 patients with 20q- carried other pathogenic GL variants in non-recurrent genes which appear to be likely coincidental. This suggests that del20q is not a SGR in response to a GL mutation, but rather a SGR due to other aforementioned mechanisms, which are currently being explored in our cohort of patients.

Graft-versus-host disease (GVHD) prophylaxis included mycophenolate mofetil and calcineurin inhibitors...A low probability of GVHD was observed (one acute GVHD II and one mild chronic GVHD). These data highlight how HSCT using low-dose Cy as part of a fludarabine-based regimen is safe and effective in SAA/non-Fanconi anaemia IBMFS.