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CTC1 variants cause Coats plus syndrome and related telomere biology disorders, presenting with multisystem vascular, calcification, and bone marrow phenotypes under an autosomal-recessive loss-of-function model, while heterozygous variants may predispose to adult-onset bone marrow failure and interstitial lung disease.
| Patient Information | Key Findings | Mutation | PMID |
|---|---|---|---|
| Child with exudative retinopathy, cerebral calcifications, duodenal atresia, preaxial polydactyly, micropenis, microcephaly, and short stature | New syndrome with normal telomere length; no CTC1 mutations detected | Not reported | PMID:23824919 |
| Boy with Norrie disease and cerebroretinal microangiopathy with calcifications and cysts | Compound heterozygous CTC1 variants | c.775G>A (p.Val259Met); c.1213delG (p.Asp405MetfsTer?) | PMID:23220793 |
| Family with adult-onset leukoencephalopathy, cerebral calcifications, and cysts | Distinct from CRMCC; no CTC1 mutations | Not reported | PMID:25034270 |
| Eight-year-old Indian boy with Coats plus syndrome, dextrocardia, and situs inversus | Homozygous CTC1 missense variant | c.1451A>C (p.His484Pro) | PMID:25928698 |
| Adolescent with CRMCC features, seizures, osteopenia | Heterozygous CTC1 mutation | c.833G>T (p.Gly278Val) | PMID:25843205 |
| Chinese family with Coats plus syndrome | Novel biallelic CTC1 missense variants | c.1A>C (p.Met1Leu); c.775G>A (p.Val259Met); c.2066A>G (p.Tyr689Cys) | PMID:29111009 |
| 23-year-old female with CRMCC and multisystem involvement | CTC1 mutations confirmed (details not specified) | Not reported | PMID:28072696 |
| Brazilian pedigree with progeroid features and recurrent bone fractures | Compound heterozygous CTC1 pathogenic variants | c.322C>T (p.Arg108Ter); c.2959C>T (p.Arg987Trp) | PMID:30393977 |
| Patient with both Coats plus syndrome and dyskeratosis congenita | Compound heterozygous CTC1 variants | Not reported | PMID:32543263 |
| 6-year-old girl with Coats plus syndrome and severe gastrointestinal bleeding | Diagnosis of Coats plus; CTC1 mutation not detailed | Not reported | PMID:35260125 |
| 15-year-old girl with Coats plus syndrome and drusenoid PEDs | CTC1 splice, missense, and nonsense variants | c.277C>T (p.Gln93Ter); c.2959C>T (p.Arg987Trp); c.3514+3A>G | PMID:36177296 |
| Two brothers with Coats plus syndrome and variable presentation | CTC1 mutation confirmed; details not specified | Not reported | PMID:35416114 |
| Adult with high-risk myelodysplastic syndrome and pulmonary fibrosis | Heterozygous CTC1 frameshift variant | c.1360del (p.Glu454SerfsTer9) | PMID:37404458 |
| 59-year-old woman with diffuse hemangiomatosis and Kasabach-Merritt syndrome | Two novel heterozygous CTC1 variants | c.435+9A>C; c.3074C>T (p.Ala1025Val) | PMID:36761951 |
| Premature infant with retinopathy initially thought ROP | Biallelic pathogenic CTC1 variants | c.724_727del (p.Lys242LeufsTer?); c.2954_2956del (p.Cys985del) | PMID:37008390 |
| 38-year-old woman with CPS presenting as capillary nonperfusion | Pathogenic CTC1 mutation | c.2954_2956del (p.Cys985del) | PMID:37974921 |
| Patient with classic dyskeratosis congenita | Compound heterozygous CTC1 mutations | p.Cys985del; c.724_727del (p.Lys242fs) | PMID:22532422 |
| Adults with acquired bone marrow failure syndromes (AA, PNH, MDS) | Heterozygous deleterious CTC1 variants identified | c.2996_2997del (p.Pro999fs); c.1213del (p.Asp405fs); c.724_727del (p.Lys242fs); c.3406G>A (p.Glu1136Lys); c.1360del (p.Glu454fs); c.3505G>A (p.Val1169Ile); c.1333C>T (p.Arg445Cys) | PMID:30891747 |
| Family with interstitial lung disease | Novel heterozygous CTC1 variant causing short telomeres | c.391G>C (p.Gly131Arg) | PMID:37978541 |
Allelic ConsistencyModerateMultiple loss-of-function and missense CTC1 variants recur in similar domains (e.g., p.Val259Met, p.Cys985del) [PMID:23220793, PMID:29111009]. Phenotypic ConsistencyWeakCTC1 mutations produce diverse phenotypes across telomere biology disorders including Coats plus, DC, bone marrow failure, and ILD. PenetranceModerateMost cases are recessive, but unaffected heterozygous carriers observed (e.g., asymptomatic father in progeroid family) [PMID:30393977]. Ethnic DiversityStrongCases reported in European, Indian, Chinese, Brazilian, Australian, and other populations. Inheritance ConsistencyWeakReports include autosomal recessive biallelic and heterozygous variants with adult-onset disease, indicating mixed inheritance patterns. Mechanism of diseaseStrongPredominantly loss-of-function CTC1 variants align with telomere maintenance failure in autosomal-recessive Coats plus and related disorders. |