Mutations in the 1A Rod Domain Segment of the Keratin 9 Gene in Epidermolytic Palmoplantar Keratoderma

Yang, J.-M.; Lee, Seewoo; Kang, H.-J.; Lee, J.-H.; Yeo, Un Cheol; Son, I.-Y.; Park, K.-B.; Steinert, Peter M.; Lee, E.-S.

doi:10.1080/000155598442674

Cited by 15 publications

(2 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…12,19,20 Autosomal dominant KRT9 mutations cause diffuse PPK, with onset at birth or early childhood (MIM 144200). 21,22 Keratins constitute the intracellular keratin filament network in keratinocytes and mutations in KRT9 might lead to the interruption of this filament network causing diffuse PPK. 21 All our four patients with KRT9 mutations had a typical KRT9 associated phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…SLURP1 mutations in two patients caused a slightly different phenotype sharing features of both Mal de Meleda (MDM; MIM 248300) and less severe diffuse PPK Gamborg‐Nielsen (GN; MIM 244850) and also aquagenic whitening 12,19,20 . Autosomal dominant KRT9 mutations cause diffuse PPK, with onset at birth or early childhood (MIM 144200) 21,22 . Keratins constitute the intracellular keratin filament network in keratinocytes and mutations in KRT9 might lead to the interruption of this filament network causing diffuse PPK 21 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hereditary palmoplantar keratoderma – phenotypes and mutations in 64 patients

Harjama

Karvonen

Kettunen

et al. 2021

Acad Dermatol Venereol

View full text Add to dashboard Cite

Background Hereditary palmoplantar keratodermas (PPK) represent a heterogeneous group of rare skin disorders with epidermal hyperkeratosis of the palms and soles, with occasional additional manifestations in other tissues. Mutations in at least 69 genes have been implicated in PPK, but further novel candidate genes and mutations are still to be found. Objectives To identify mutations underlying PPK in a cohort of 64 patients. Methods DNA of 48 patients was analysed on a custom‐designed in‐house panel for 35 PPK genes, and 16 patients were investigated by a diagnostic genetic laboratory either by whole‐exome sequencing, gene panels or targeted single‐gene sequencing. Results Of the 64 PPK patients, 32 had diffuse (50%), 19 focal (30%) and 13 punctate (20%) PPK. None had striate PPK. Pathogenic mutations in altogether five genes were identified in 31 of 64 (48%) patients, the majority (22/31) with diffuse PPK. Of them, 11 had a mutation in AQP5, five in SERPINB7, four in KRT9 and two in SLURP1. AAGAB mutations were found in nine punctate PPK patients. New mutations were identified in KRT9 and AAGAB. No pathogenic mutations were detected in focal PPK. Variants of uncertain significance (VUS) in PPK‐associated and other genes were observed in 21 patients that might explain their PPK. No suggestive pathogenic variants were found for 12 patients. Conclusions Diffuse PPK was the most common (50%) and striate PPK was not observed. We identified pathogenic mutations in 48% of our PPK patients, mainly in five genes: AQP5, AAGAB, KRT9, SERPINB7 and SLURP1.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hereditary palmoplantar keratoderma – phenotypes and mutations in 64 patients

Harjama

Karvonen

Kettunen

et al. 2021

Acad Dermatol Venereol

View full text Add to dashboard Cite

show abstract

Epidermolytic palmoplantar keratoderma of Vörner: re-evaluation of Vörner's original family and identification of a novel keratin 9 mutation

Küster¹,

Reis

Hennies

2002

Arch Dermatol Res

View full text Add to dashboard Cite

In 1901, Hans Vörner observed a family with a diffuse non-transgredient palmoplantar keratoderma of autosomal dominant inheritance. Histopathologically, he found epidermolytic hyperkeratosis as a characteristic sign and diagnostic criterion of this disorder. We performed a follow-up study of the family originally seen by Vörner in 1901 with clinical, histopathological, and molecular investigations. Clinically, affected family members showed the typical diffuse keratoses over the entire surface of the palms and soles sharply bordered by red margins. A mycotic infection was additionally found in two patients examined. Histopathological investigations confirmed epidermolytic hyperkeratosis. Molecular studies revealed a novel mutation in keratin 9, N160I, in patients from the family. The mutation in the coil-1A domain is thought to have a dominant negative effect on the assembly of keratin intermediate filaments, explaining the dominant inheritance of the phenotype. These findings give further evidence that palmoplantar keratoderma of Vörner represents the same entity as palmoplantar keratoderma of Thost, which was recently re-evaluated in Thost's original family and shown to be caused by a similar mutation, R162 W, in the same segment of keratin 9.

show abstract

A novel mutation of keratin 9 gene (R162P) in a Japanese family with epidermolytic palmoplantar keratoderma

et al. 2004

View full text Add to dashboard Cite

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited skin disorder characterized by hyperkeratosis of the skin over the palms and soles. Mutations in keratin 9 gene (KRT9) have been demonstrated in EPPK. In this study, we screened a Japanese family with EPPK for KRT9 mutation by polymerase chain reaction amplification of genomic sequences, followed by heteroduplex analysis and direct nucleotide sequencing. The mutation consisted of a G-to-C transversion at codon 162 in exon 1, which was located in the hot spot of the mutations that have been reported previously (R162Q and R162W). However, the amino acid substitution was proline for arginine (R162P) in the 1A rod domain, the highly conserved helix initiation motif of keratin 9. Our result illustrates the repertoire of KRT9 mutation underlying the occurrence of EPPK in a Japanese family and is an important contribution to the investigation of the genotype/phenotype correlation.

show abstract

Mutations in the 1A Rod Domain Segment of the Keratin 9 Gene in Epidermolytic Palmoplantar Keratoderma

Cited by 15 publications

References 17 publications

Hereditary palmoplantar keratoderma – phenotypes and mutations in 64 patients

Hereditary palmoplantar keratoderma – phenotypes and mutations in 64 patients

Epidermolytic palmoplantar keratoderma of Vörner: re-evaluation of Vörner's original family and identification of a novel keratin 9 mutation

A novel mutation of keratin 9 gene (R162P) in a Japanese family with epidermolytic palmoplantar keratoderma

Contact Info

Product

Resources

About