Table 1:
Table summarizing demographics, clinical features, associated genomic variants & outcomes for our cohort of patients with short telomere syndromes.
| Case no. | Age at symptom onset/Gender | Diagnosis | Organ system manifestations | Flow-FISH results [centile telomere lengths in granulocytes/ly mphocytes] | Genomic aberration identified | Zygosity | Minor Allelic requency | SIFT/Polyphen2 predictions | Sequencing approach | HSCT | SOT; type | Others treatments | Best response to treatment | Progression to AML | Comments | At OS (95% CI) 182 months (113, not reached), death status/age at death in years | Cause of death |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2/F | DKC | Bone marrow failure, liver cirrhosis, IIP | N/A | N/A | N/A | N/A | N/A | - | Yes | No | Danazol | None | No | Diagnosed elsewhere | Dead/17 | End-stage cirrhosis |
| 2 | 64/F | STS | Bone marrow failure, ILD (NSIP) | <1st centile/ <1st centile | TERT, exon 12, missense, H983T amino acid substitution | N/A | N/A | N/A | - | No | No | No | - | No | - | Dead/66 | Acute exacerbation of IIP |
| 3 | 57/M | STS | Bone marrow failure, cirrhosis, IIP | <1st centile/ <1st centile | Not tested | N/A | N/A | N/A | - | No | No | No | - | No | - | Alive/57 | - |
| 4 | 54/M | STS | IIP (Unclassifiable) | <1st centile/ <1st centile | TERT VUS c.2030G>A,p.G677D | Heterozygous | 0% | Deleterious/Prob. Damaging | NGS | No | Yes/Lung | Danazol | Mild improvement in WBC count | No | - | Alive/60 | - |
| 5 | 63/M | STS | IIP (UIP) | <1st centile/1-10th centile | Ongoing | N/A | N/A | N/A | NGS | No | Yes/Lung | No | - | No | Pirfenidone used for IIP; grade A1 allograft rejection, managed with prednisone | Alive/66 | - |
| 6 | 47/M | STS | IIP (UIP) | <1st centile/ <1st centile | Ongoing | N/A | N/A | N/A | WES ongoing | No | Yes/Lung | No | - | No | Grade A2 allograft rejection, managed with prednisone | Alive/49 | - |
| 7 | 62/F | STS | IIP (Pleuroparenchymal fibroelastosis) | <1st centile/ 1-10th centile | RTEL VUS c.101A>G, p.Q34R | Heterozygous | N/A | Tolerated/Benign | NGS | No | Yes/Lung | No | - | No | Grade A2 rejection managed with prednisone; developed SCC of skin & tongue around 17 years before diagnosis | Alive/64 | - |
| 8 | 56/M | STS | IIP (UIP) | <1st centile/ 1-10th centile | Not identified | N/A | N/A | N/A | NGS | No | Yes/Lung | No | - | No | - | Alive/63 | - |
| 9 | 74/M | STS | IIP, bone marrow failure | <1st centile/ <1st centile | N/A | N/A | N/A | N/A | - | - | - | - | - | - | Developed SCC of skin | - | - |
| 10 | 56/M | STS | IIP (NSIP), macrocytosis without anemia | <1st centile/ <1st centile | N/A | N/A | N/A | N/A | - | - | - | - | - | - | Lost to follow-up | Alive/57 | - |
| 11 | 53/M | STS | NRH, IIP (UIP), macrocytosis without anemia | N/A; documented short telomeres | N/A | N/A | N/A | N/A | N/A | No | No | No | - | - | N-acetylcysteine used. | Dead/63 | Acute exacerbation of IIP |
| 12 | 4/M | DKC | Bone marrow failure with transfusion dependence | Not done | DKC1 (Variant details N/A) | N/A | N/A | N/A | NGS | Yes, details not available | No | Danazol | None | - | Classic DKC phenotype of oral leukoplakia, narrow tear ducts & lacy skin pigmentation | Alive/30 | - |
| 13 | 58/M | STS | Bone marrow failure, IIP | Not done | TERC (n.214G>C, noncoding variant) | Heterozygous | 0% | N/A | NGS | Yes | No | No | - | - | Progressed to MDS-EB-2; developed SCC of skin | Dead/59 | Complications from allogeneic HSCT |
| 14 | 17/M | DKC | Bone marrow failure | <1st centile/ <1st centile | TERTc.2768C >T; p.P923L; CSF3R VUS c.2422G>A; p. G808K | TERT: Heterozygous CSF3R: Heterozygous | TERT: 0.00041% CSF3R:0.62% | TERT: Deleterious/Prob. Damaging CSF3R: Deleterious/Prob. Damaging | NGS | No | No | Immunosuppressive treatment with ATG & cyclosporine | Mild improvement in platelet count | No | Being considered for allogeneic PBSCT; cytogenetic abnormalities show del(7)(q22). | Alive/81 | - |
| 15 | 63/M | STS | Bone marrow failure, IIP (unclassifiable) | <1st centile/ <1st centile | - | - | - | - | WES | No | No | Danazol | None | No | Developing complications from IIP | Alive/67 | - |
| 16 | 66/M | STS | Cryptogenic cirrhosis, IIP (unclassifiable), Bone marrow Failure | <1st centile/ <1st centile | Ongoing | N/A | N/A | N/A | WES Ongoing | No | No | No | - | No | End-stage cryptogenic cirrhosis | Alive/68 | - |
| 17 | 60/M | STS | Crytpogenic cirrhosis, IIP (with combined emphysemato us changes) | <1st centile/ <1st centile | Ongoing | N/A | N/A | N/A | WES ongoing | No | No | No | - | No | Alive/61 | - |
FISH=Fluorescence in-situ hybridization; HSCT=Allogeneic Hematopoietic Stem Cell Transplantation; SOT=Solid organ transplant; IIP=Idiopathic interstitial pneumonia; NSIP=Non-specific interstitial pneumonia; UIP=Usual interstitial pneumonia; N/A=Not available; NGS=Next generation sequencing; WES=Whole exome sequencing panel; SCC=squamous cell cancer.