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| Bone Marrow Failure v1.21 | TYMS | Zornitza Stark Tag digenic tag was added to gene: TYMS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v1.21 | TYMS | Zornitza Stark Phenotypes for gene: TYMS were changed from Dyskeratosis congenita MONDO:0015780 to Dyskeratosis congenita, digenic, MIM#620040 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v1.20 | TYMS | Zornitza Stark edited their review of gene: TYMS: Changed phenotypes: Dyskeratosis congenita, digenic, MIM#620040 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v1.19 | TYMS | Zornitza Stark Marked gene: TYMS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v1.19 | TYMS | Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v1.19 | TYMS | Zornitza Stark Classified gene: TYMS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v1.19 | TYMS | Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v1.18 | TYMS | Zornitza Stark reviewed gene: TYMS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskeratosis congenita MONDO:0015780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v1.18 | TYMS |
Lucy Spencer gene: TYMS was added gene: TYMS was added to Bone Marrow Failure. Sources: Literature Mode of inheritance for gene: TYMS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TYMS were set to 35931051 Phenotypes for gene: TYMS were set to Dyskeratosis congenita MONDO:0015780 Review for gene: TYMS was set to RED Added comment: 8 families with dyskeratosis congenita and heterozygous variants in TYMS. 4 PTCs, 2 missense and 1 splice (2 families had the same frameshift). However in all families 1 unaffected parent was also heterozygous for the same TYSM variant. The other parent in 3 of these families was then shown to carry a heterozygous variant in ENOSF1 which each affected child was also heterozygous for. ENOSF1 has been shown to modify TYMS expression at the RNA level by acting as an antisense molecule to TYMS. ENOSF1 partially overlaps TYMS on chromosome 18 and is transcribed in the opposite direction to TYMS. This paper is suggesting digenic inheritance. The TYMS wild type parent from another family was seen to have a TYMSOS variant which was also observed along with the TYMS variant in their 2 affected children. Immunoblotting showed a stark reduction in TYMS protein level in the cells of affected probands when compared to the parent carrier, wild-type parent, and the controls. Lymphoblastoid cells from affected probands have severe TYMS deficiency, altered cellular deoxyribonucleotide triphosphate pools, and hypersensitivity to the TYMS-specific inhibitor 5-fluorouracil. These defects in the nucleotide metabolism pathway resulted in genotoxic stress, defective transcription, and abnormal telomere maintenance. Gene-rescue studies in cells from affected probands revealed that post-transcriptional epistatic silencing of TYMS is occurring via elevated ENOSF1. Sources: Literature |
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