Mosaic skin disorders - deep sequencing

Gene: PMVK

Green List (high evidence)

Comment on list classification: There are 3 unrelated individuals diagnosed with linear porokeratosis / ILVEN with mosaic PMVK variants. 1 individual harboured a mosaic PMVK variant only (vPMID: 38360177), while two patients carried a germline PMVK mutation together with either a somatic PMVK variant, or evidence of loss of heterozygosity (PMID: 30942823). Based on the available evidence, this gene should be promoted to Green for Mosaic skin disorders - deep sequencing.

Created: 3 Dec 2025, 11:50 a.m. | Last Modified: 3 Dec 2025, 11:50 a.m.

Panel Version: 3.9

PMID: 38360177 Polubothu et al., 2024
Patient with Inflammatory linear verrucous epidermal nevus (ILVEN) reported to carry a de novo PMVK variant c.126delG, p.R42fs (NM_006556.4: c.124del, p.Arg42Glyfs*16) - not in gnomAD v4.1.0; method: 250x WES; mosaic in blood and skin, no second variant detected in the same gene in skin.

PMID: 30942823 Atzmony et al., 2019 / PMID: 35853659 Atzmony et al., 2022
Report of 2 patients with Linear Porokeratosis - plaques distributed along the lines of Blaschko, suggesting cutaneous mosaicism. Inheritance pattern unknown.
Patient 1: 20 yo man with a germline-heterozygous PMVK c.329G>A, p.R110Q mutation in blood & affected skin. Skin showed a higher mutant allele fraction (Ref:Non-Ref read ratio was 21:15 in blood and 16:61 in tissue). Suggested somatic loss-of-heterozygosity.
Patient 2: 5 yo girl with a germline mutation PMVK c.79G>T, p.Glu27* & a somatic mutation PMVK c.379C>T, p.Gln127* (Ref:Non-Ref = 113:0 in blood, and 119:34 in tissue). Variant p.Glu27* has MAF = 0.0005930 in gnomAD v4.1.0 (Admixed American pop), no homozygotes.

This gene is NOT predicted to be LoF intolerant (pLI = 0.02, LOEUF = 0.87). PMVK is associated with AD Porokeratosis 1, multiple types MIM:175800 in OMIM (accessed 3rd Dec 2025).

Created: 3 Dec 2025, 11:01 a.m. | Last Modified: 3 Dec 2025, 11:55 a.m.

Panel Version: 3.9

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
inflammatory linear verrucous epidermal nevus, MONDO:0019318; Porokeratosis 1, multiple types OMIM:175800

Publications

• 30942823
• 35853659
• 38360177

Green List (high evidence)

Mosaic

Created: 31 Oct 2025, 2:01 p.m. | Last Modified: 31 Oct 2025, 2:01 p.m.

Panel Version: 3.1

Mode of inheritance
Other

Phenotypes
Inflammatory Linear Verrucous Epidermal Naevi (ILVEN)

Publications

• PMID: 38360177
• PMID: 35853659

I don't know

Heterozygous germline variants + second somatic hit (point mutation or LOH) in affected tissues.

Created: 5 Dec 2019, 3:40 p.m. | Last Modified: 5 Dec 2019, 3:40 p.m.

Panel Version: 0.16

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Linear porokeratosis

Publications

• 30942823