A novel MVK missense mutation in one Chinese family with disseminated superficial actinic porokeratosis

Abstract

Disseminated superficial actinic porokeratosis (DSAP) is a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. mevalonate kinase, (MVK) a gene know to play an important role in regulation of calcium-induced keratinocyte differentiation and proliferation, has recently been suggested as the disease-causing gene for DSAP. Here we report a direct sequencing analysis of this gene in 3 DSAP families, 6 sporadic cases, and 100 unrelated healthy controls. We detected a heterozygous T to A transition at nucleotide 205 in exon 3 of MVK gene in one familial case. This mutation will result in an amino acid change at codon 69 (P.Ser69Thr), which is from a serine codon (TCA) to a threonine codon (ACA). No such mutation was detected in the unaffected family members or the 100 unrelated healthy controls. Our results demonstrated a novel missense mutation in MVK gene. This will be valuable for the diagnosis of DSAP as well as for genetic counseling and prenatal diagnosis of affected families.

Twists and turns of the genetic story of mevalonate kinase-associated diseases: A review

“…Since then, several other DSAP patients with different germline MVK mutations have been reported. 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 In 2015, and confirmed later, heterozygous germline mutations in genes encoding three other enzymes downstream of MK in the mevalonate pathway (i.e., mevalonate diphosphodecarboxylase [ MVD ], phosphomevalonate kinase, and farnesyl diphosphate synthase) were also found to cause DSAP and other PK subtypes ( Fig. 2 ).…”

Two Novel and Three Recurrent Mutations in the Mevalonate Pathway Genes in Chinese Patients with Porokeratosis

“…Exposure to ultraviolet, genetic susceptibility, immunosuppression, radiation, drugs and viral infections were considered risk factors for PK. [7][8][9][10][11] In 2012, mutations in MVK, a mevalonate pathway gene, were identified as causative genes for DSAP. Subsequently, other mevalonate pathway genes, including FDPS, MVD, and PMVK, have been associated with PK.…”

Hyper-IgD syndrome/mevalonate kinase deficiency: what is new?

“…Heterozygous mutations in MVK were identified by exome sequencing in several familial and sporadic DSAP cases [ 41 – 43 ]. Several more case reports have since appeared [ 44 – 46 ], all of them from patients of Asiatic origin. Although some of the mutations identified have also been found in MKD, most mutations were splice site mutations, the studied DSAP patients did not show any clinical signs of MKD, and porokeratosis is not a known feature of MKD [ 41 , 44 ].…”

“…Several more case reports have since appeared [ 44 – 46 ], all of them from patients of Asiatic origin. Although some of the mutations identified have also been found in MKD, most mutations were splice site mutations, the studied DSAP patients did not show any clinical signs of MKD, and porokeratosis is not a known feature of MKD [ 41 , 44 ]. In DSAP, no abnormal IgD serum levels have been described [ 41 ].…”