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Review
. 2019 Nov;7(11):e977.
doi: 10.1002/mgg3.977. Epub 2019 Sep 16.

Keratin 9 L164P mutation in a Chinese pedigree with epidermolytic palmoplantar keratoderma, cytokeratin analysis, and literature review

Xiaoliang Liu  1 , Chuang Qiu  2 , Rong He  1 , Yuanyuan Zhang  1 , Yanyan Zhao  1
Affiliations
Review

Keratin 9 L164P mutation in a Chinese pedigree with epidermolytic palmoplantar keratoderma, cytokeratin analysis, and literature review

Xiaoliang Liu et al. Mol Genet Genomic Med. 2019 Nov.

Abstract

Background: Epidermolytic palmoplantar keratoderma (EPPK) is characterized by hyperkeratotic lesions on palms and soles. The disorder is caused by mutations of keratin 9 (KRT9) or KRT1 gene.

Methods: Epidermolytic palmoplantar keratoderma was diagnosed by physical examination and histopathological analysis in a five-generation Chinese family. Mutation was screened by Sanger sequencing. The palmar expression of multiple cytokeratins were analyzed by tape-stripping and Real-time PCR. Literatures of EPPK with additional symptoms were reviewed.

Results: Affected family members showed diffuse palmoplantar keratosis, with knuckle pads, friction-related lesions and a novel additional symptom of palmar constriction. A heterozygous mutation of c.T491C (p.L164P) of KRT9 was found within the helix initiation motif. The hydrophobic effect was decreased and the initiation of coiled-coil conformation was delayed. The KRT16/KRT6 expression were significantly increased in the patients, especially on the right, indicating activation of stress-response and wound-healing cytokeratins. There were also increased KRT9/KRT2, unchanged KRT10/KRT1, and undetectable KRT14/KRT5 expression. The genetic and phenotypic heterogeneity of EPPK with additional symptoms were summarized by literature review.

Conclusion: The p.L164P mutation of KRT9 caused EPPK with a novel symptom of palmar constriction. The expression of multiple cytokeratins was altered in EPPK patients.

Keywords: EPPK; KRT9; cytokeratin; intermediate filament; mutation.

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Conflict of interest statement

The authors stated no conflict of interest.

Figures

Figure 1
Figure 1
(a) Pedigree of the EPPK family. (b) Clinical presentation. There were diffuse yellowish thickening with erythematous margins on the palms and soles. Palm hyperkeratosis and knuckle pads were more severe on the right. The right palm was smaller than the left. (c) Histological presentation. The arrows indicate vacuolated cells. The bar represents 50 μm in image of ×400. (d) Sanger sequencing of the KRT9 gene. The heterozygous variation in c.T491C (p.L164P) was found in the patient, not in the control
Figure 2
Figure 2
(a) Both wild‐type and mutant KRT9 were detectable in the patient, not in the control by Taqman method of Real‐time PCR. (b) Relative expression of KRT9/KRT2, KRT16/KRT6, and KRT10/KRT1 were assayed by quantitative Real‐time PCR, with the β‐actin mRNA as internal control. The bars are graphed as mean ± SD of fold over control left that is taken as “1.” Each sample was amplified in triplicates for at least three independent experiments. *: p < .05 compared with the control; **: p < .01 compared with the control; #: p < .01 compared with the left
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