Molecular epidemiology of pachyonychia congenita in the Israeli population

Pavlovsky, Mor; Peled, A.; Samuelov, Liat; Malki, Liron; Malovitski, Kiril; Assaf, Sari; Mohamad, Janan; Meijers, Odile; Eskin‐Schwartz, Marina; Sarig, Ofer; Sprecher, Eli

doi:10.1111/ced.14509

Cited by 3 publications

(1 citation statement)

References 26 publications

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“…Relative reports found that various keratin mutations cause several cutaneous disorders, with PC arising from mutations in KRT6A, KRT6B, KRT6C, KRT16, and KRT17 genes. 8 Keratin 16 is mainly expressed in the palmoplantar epidermis. Structurally, the keratin comprises α-helical rod domains and non-helical linkers and can be divided into four parts (domain 1A, 1B, 2A, and 2B), respectively.…”

Section: Discussionmentioning

confidence: 99%

Mutation p.Arg127Pro in the 1A Domain of KRT16 Causes Pachyonychia Congenita in Chinese Patient: A Case Report of PC Associated with Acral Melanoma

Ge,

Chen,

Chou

et al. 2024

CCID

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Pachyonychia congenita (PC) is a group of rare hereditary disorders, characterised by hypertrophic nails and palmoplantar keratoderma (PPK), particularly localised to the pressure areas of the feet. At a molecular level, it is caused by mutations in genes encoding KRT6A, KRT6B, KRT6C, KRT16, or KRT17. To identify the underlying gene mutation in a Chinese family with PC presenting with disabling palmoplantar keratoderma and subsequent associated acral melanoma. Genomic DNA was extracted from peripheral blood samples of three available individuals in the Chinese family, which included the patient and his two unaffected sisters. The index patient presented with severe palmoplantar keratoderma as well as a newly diagnosed acral malignant melanoma (MM). Whole-exome sequencing (WES) was carried out with amplification of exon 1 of KRT16 by polymerase chain reaction (PCR). PCR products were then sequenced to identify potential mutations. We identified the proline substitution mutation p.Arg127Pro (c.380G>C) in our patient’s 1A domain of KRT16. The same mutation was not found in his sisters or unrelated healthy controls. The mutation (p.Arg127Pro (c.380G>C)) in KRT16 has been reported in Dutch patients with PC. However, it is the first such report of a patient with a PC of Chinese origin. In addition, the acral MM occurred under the background of genetic PPK caused by KRT16 mutation in this patient.

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Section: Discussionmentioning

confidence: 99%

Mutation p.Arg127Pro in the 1A Domain of KRT16 Causes Pachyonychia Congenita in Chinese Patient: A Case Report of PC Associated with Acral Melanoma

Ge,

Chen,

Chou

et al. 2024

CCID

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KERATIN 17-related recessive atypical pachyonychia congenita with variable hair and tooth anomalies

et al. 2022

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The variant c.274A>G (p.Asn92Asp) in KRT17 in a patient with pachyonychia congenita and a novel clinical feature of acne inversa

Wang,

Zhu,

Dong

et al. 2024

Front. Genet.

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IntroductionThe occurrence of pachyonychia congenita (PC) and acne inversa (AI) may be related to gene mutations. The aim of this study is to identify the genetic cause in a patient with PC and AI, and to explore the possible molecular mechanism of their co-occurrence.MethodsThe clinical data of the proband were collected, and the genomic DNA of the proband and unaffected parents were extracted. The variant sites of the proband were identified by whole-exome sequencing, and then the variant sites of the proband and his parents were verified by Sanger sequencing.ResultsA heterozygous variant in KRT17 gene was found in the patient, resulting in a missense amino acid variant (p.N92D). The variant was not found in his parents or 100 unrelated healthy controls. In addition, this variant was not found in the gnomad v4 database. The three-dimensional structure analysis of the protein suggested that the polarity of amino acids changed after the variant. After lentiviral plasmid transfection into HaCaT cells, the expression level of NOTCH signaling decreased in the constructed c.274A>G (p.Asn92Asp) of KRT-17 mutant cells compared to that in the wild-type. Subsequent verification confirmed that differences in the expression levels of p-PI3K, AKT and p-AKT between the groups were not statistically significant.DiscussionAlthough this variant has been reported previously, our findings could expand the spectrum of co-occurrence of PC and AI with KRT17 gene variants, and elucidated the possible pathogenesis at the protein level, thereby laying a foundation for the genetic diagnosis and genetic counseling provided to individuals with PC.

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Molecular epidemiology of pachyonychia congenita in the Israeli population

Cited by 3 publications

References 26 publications

Mutation p.Arg127Pro in the 1A Domain of KRT16 Causes Pachyonychia Congenita in Chinese Patient: A Case Report of PC Associated with Acral Melanoma

Mutation p.Arg127Pro in the 1A Domain of KRT16 Causes Pachyonychia Congenita in Chinese Patient: A Case Report of PC Associated with Acral Melanoma

KERATIN 17-related recessive atypical pachyonychia congenita with variable hair and tooth anomalies

The variant c.274A>G (p.Asn92Asp) in KRT17 in a patient with pachyonychia congenita and a novel clinical feature of acne inversa

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