CPUM_TYMS
- Gene
- TYMS
- Disease
- CPUM
- Inheritance
- AR
- Classification
- Limited
- Total Score
- 1.5
- Publications Reviewed
- 1
- Publication Span
- 0.43 years
- Last Updated
- 08/14/2025
- Curator(s)
- Macayla Weiner, Harriet Dashnow
Description
A biallelic intronic GATGGT repeat expansion in TYMS was reported in monozygotic twin girls with congenital progressive universal melanosis (CPUM), a congenital, progressive, diffuse hyperpigmentation phenotype without other accompanying symptoms. Long-read whole-genome sequencing and STR analysis identified 210-259 repeat units in both affected twins; each unaffected parent was heterozygous for an expanded allele, and 236 controls had repeat sizes up to 172 units [@pmid:40589716].
Genetic evidence
Total: 1.5
| Singular Evidence | Probands | PMID:40589716 | 1.5 | One non-consanguineous family with monozygotic twin probands with CPUM. Both affected twins carried biallelic intronic TYMS GATGGT expansions (210-259 repeat units), while each unaffected parent was heterozygous for an expanded allele, consistent with autosomal recessive inheritance; 236 controls had repeat sizes <=172 units and no biallelic expansions. |
1 rows
Experimental evidence
Total: 0
| Function | Regulatory impact | PMID:40589716 | 0 | RT-qPCR and western blotting did not show a consistent regulatory effect of the TYMS repeat expansion in available patient-derived samples. TYMS mRNA levels in PBMCs and cultured skin fibroblasts from the twins were within control ranges, and fibroblast TYMS protein levels varied between twins but remained within the control range. Methylation analysis identified DMRs, but significant enrichments were not related to skin pigmentation or melanogenesis. |
1 rows
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.