Mosaic skin disorders - deep sequencing

Gene: MVK

Green List (high evidence)

Comment on list classification: There are at least 9 unrelated families reported in literature with porokeratosis / disseminated superficial actinic porokeratosis (DSAP), with heterozygous germline mutations in MVK, with confirmed postnatal second-hit mosaic MVK mutation in 2 cases. Other genes in the pathway have been implicated in porokeratosis. Based on available evidence, this gene should be promoted to Green for Mosaic skin disorders - deep sequencing.

Created: 31 Dec 2025, 4:40 p.m. | Last Modified: 31 Dec 2025, 4:40 p.m.

Panel Version: 3.25

PMID: 39386107 Zhao et al., 2024
Epidermal second-hit mutation in MVK gene associated with linear porokeratosis. Reported a case of 6-year-old boy diagnosed with linear porokeratosis and a germline heterozygous MVK c.389_394del: p.D130_I131del mutation, along with somatic LOH confined to the lesional epidermis. Father, heterozygous for the germline MVK mutation, was unaffected. The MVK c.389_394del mutation was shown to be mosaic in affected skin lesions (59% mutant vs 41% WT).
Method: panel sequencing targeting ∼500 causative genes of genodermatoses on DNA.

PMID: 31753123 Atzmony et al., 2019
Authors pose that biallelic mutations are needed to cause mevalonate kinase deficiency (MKD), with mevalonic aciduria and hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) being on the MKD spectrum (HIDS being the milder presentation, and mevalonic aciduria on the severe end). Other genes in the pathway have been implicated in porokeratosis: MVD, PMVK and FDPS.

PMID: 31207227 Kubo et al., 2019
DSAP7 - Japanese patient with disseminated superficial actinic porokeratosis - Heterozygote of MVK c.1073A>C (p.Q358P) mutation with two postnatal second-hit epidermis specific mutations in MVK: c.575G>A and c.602C>T.

PMID: 26794421 Liu et al., 2016
Report of three mutations in the MVK gene in six sporadic cases with disseminated superficial actinic porokeratosis (DSAP). Method: direct sequencing of MVK. Variants detected: p.Gly335Asp, p.Pro11Ser, p.Gly376Ser. All three mutations were shown to reduce protein stability compared to WT.

PMID: 22983302 Zhang et al., 2012
Family with 3 affected individuals with DSAP, heterozygous for MVK c.764T>C, p.Leu255Pro. Unaffected family members did not carry the mutation. Method: exome seq + linkage analysis.

MVK is associated with AD Porokeratosis 3, multiple types, OMIM:175900 (OMIM accessed 31st Dec 2025).
Sources: Literature

Created: 31 Dec 2025, 4:34 p.m. | Last Modified: 31 Dec 2025, 4:34 p.m.

Panel Version: 3.22

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Porokeratosis 3, multiple types, OMIM:175900; porokeratosis 3, disseminated superficial actinic type, MONDO:0008293

Publications

• 22983302
• 26794421
• 31207227
• 31753123
• 39386107

Red List (low evidence)

?No evidence of mosaicism in this paper (or others that I've seen) - seem to be dominant pedigrees.

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
Actinic porokeratosis; porokeratosis of Mibelli (175900)

Publications

• 24781643

Green List (high evidence)

This gene was part of an initial gene list collated by Thomas Cullup, GOSH and Veronica Kinsler, UCL, 25.Jan.2019 on behalf of the GMS Skin Specialist Test Group. Gene Symbol submitted: MVK; Suggested initial gene rating: Green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.

Created: 31 Jan 2019, 2:50 p.m.