Curation CPUM TYMS

Gene TYMS

Disease CPUM

Inheritance AR

Score

1.5 + 0 = 1.5 / 18

Genetic + experimental = total

Classification

Limited

Refuted

Moderate

Definitive

Last Updated 08/14/2025

Pubs Reviewed 1

Publication Span 0.43 years

Publication Interval 0.43 years

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 units¹.

All criTRia Curations Locus Page

Genetic evidence

Total: 1.5

Per page

Category	Type	Citation	Score	Details
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.

Experimental evidence

Total: 0

Per page

Category	Type	Citation	Score	Details
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.

References

Direct supporting references for info on this page.

Intronic hexanucleotide repeat expansion in

Sunisa,Kanchanasutthiyakorn, Sakchai,Chaiyamahapurk, Siraprapa,Tongkobpetch, Kanokwan,Santawong, Chalurmpon,Srichomthong, Tippayakarn,Klomchan, Chaiyaporn,Virochsangaroon, Monnat,Pongpanich, Prateep,Warnnissorn, Sutatip,Pongcharoen, Vorasuk,Shotelersuk

Biomedical reports · 2025-06-12

pmid:40589716

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.