Ectodermal dysplasia

Gene: TUFT1

Green List (high evidence)

Comment on list classification: As there are now 11 individuals from 4 unrelated families reported in literature (including 2 families with the same founder variant), there is enough evidence to promote TUFT1 to Green for Ectodermal dysplasia at the next GMS update. This association is supported by a knockout mouse model that recapitulates the human phenotype (PMID: 37716648).

Created: 7 Nov 2025, 5:17 p.m. | Last Modified: 7 Nov 2025, 5:17 p.m.

Panel Version: 4.15

PMID: 36689522 Jackson et al., 2023
Report of 9 individuals from 3 families with woolly hair and skin fragility, homozygous for either c.60+1G>A (Irish founder variant) or p.Gln189Asnfs*49. No dental abnormalities.

PMID: 37716648 Verkerk et al., 2024
Report of two Dutch siblings with mild skin fragility, woolly hair, and mild palmoplantar keratoderma. Both sibs harboured a homozygous splice-site variant in the TUFT1 gene. The teeth were all present and had a normal appearance, though susceptibility to caries was noted. WES identified a homozygous splice acceptor site variant in intron 8, c.724-2A>G in TUFT1.
A Tuft1-knockout mouse model mimicked the patients' phenotypes: KO mice showed abnormal fur with a wavy appearance mimicking the woolly hair phenotype; 40% of KO mice developed spontaneous skin erosions.

This gene is associated with AR Woolly hair-skin fragility syndrome, OMIM:620415 (accessed 7th Nov 2025).

Created: 7 Nov 2025, 5:11 p.m. | Last Modified: 7 Nov 2025, 5:15 p.m.

Panel Version: 4.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Woolly hair-skin fragility syndrome, OMIM:620415

Publications

• 36689522
• 37716648

I don't know

Comment on list classification: This gene should be rated AMBER despite having three unrelated cases, as the variant found in two families is a founder variant in the Irish population.

Created: 1 Jun 2023, 6:46 p.m. | Last Modified: 1 Jun 2023, 6:46 p.m.

Panel Version: 3.3

PMID:36689522 reported nine individuals from three different families with biallelic variants in TUFT1 gene and presenting with woolly hair and skin fragility. One donor splice-site variant, c.60+1G>A, was present in two families, while a frameshift variant, p.Gln189Asnfs*49, was found in the third family. Haplotype analysis showed the c.60+1G>A variant is a founder variant in the Irish population. This is also supported by functional studies, mainly expression studies.

This gene has not yet been associated with any phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature

Created: 1 Jun 2023, 6:44 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ectodermal dysplasia syndrome, MONDO:0019287

Publications

• 36689522