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Maedica Jun 2017Pachyonychia congenita (PC) is a rare autosomal dominant skin disorder, with unknown prevalence, although it is estimated there are between 2,000 and 10,000 cases of PC...
Pachyonychia congenita (PC) is a rare autosomal dominant skin disorder, with unknown prevalence, although it is estimated there are between 2,000 and 10,000 cases of PC worldwide. The International PC Research Registry (IPCRR) has currently identified (as of November 2016) 746 individuals (in 403 families) with genetically confirmed PC. Heterozygous mutations, predominantly missense mutations, in any one of five keratin genes, KRT6A, KRT6B, KRT6C, KRT16, or KRT17 cause PC. The predominant clinical findings include plantar keratoderma, plantar pain and variable dystrophy of some or all toenails and/ or fingernails. Oral leukokeratosis, follicular hyperkeratosis, cysts of various types and natal teeth may also be present. We report the first case of genetically confirmed PC from Romania due to a mutation in KRT6A, p.Arg466Pro.
PubMed: 29090033
DOI: No ID Found -
The British Journal of Dermatology May 2017The International Pachyonychia Congenita Consortium (IPCC) is a group of physicians and scientists from around the world dedicated to developing therapies for...
The International Pachyonychia Congenita Consortium (IPCC) is a group of physicians and scientists from around the world dedicated to developing therapies for pachyonychia congenita, a rare autosomal dominant skin disorder. The research presented at the 13th Annual Research Symposium of the IPCC, held on 10-11 May 2016, in Scottsdale, AZ, U.S.A., is reported here.
PubMed: 28345191
DOI: 10.1111/bjd.15417 -
Biomedicines Apr 2022Pachyonychia congenita (PC) is a genodermatosis associated with severe painful palmoplantar keratoderma (PPK) and thickened dystrophic nails caused by autosomal...
Pachyonychia congenita (PC) is a genodermatosis associated with severe painful palmoplantar keratoderma (PPK) and thickened dystrophic nails caused by autosomal dominant-negative mutations in five genes encoding keratins 6A-B-C, 16, and 17. The mechanical, surgical, or medical options for painful PC are inefficient. Given ErbB/Her family members' role in epidermal homeostasis, this study sought to investigate the possibility of treating PC patients with PPK by blocking signaling either with EGFR (Her1) inhibitor erlotinib or lapatinib, a dual EGFR(Her1)/Her2. After 1 month of therapy with oral erlotinib treatment at 75 mg/day, the pain disappeared for patient #1, with partially reduced hyperkeratosis, while increasing the dose to 100 mg/day resulted in painful skin fissures. Therapy replacement with erlotinib cream at 0.2% was inconclusive, and substitution with oral lapatinib at alternating doses of 500 and 750 mg/day achieved a good compromise between pain reduction, symptom improvements, and side effects. Patient #2's treatment with erlotinib cream failed to display significant improvements. Oral erlotinib started at 75 mg/day then reduced to 25 mg/day because of the formation of an acneiform rash. Treatment considerably improved the patient's condition, with an almost complete disappearance of pain. Oral Her1 or 1/2 inhibitors reduced pain, improved two PC patients' quality of life, and offered promising therapeutic perspectives.
PubMed: 35453591
DOI: 10.3390/biomedicines10040841 -
Experimental Dermatology Jun 2018The type I intermediate filament keratin 16 (K16) is constitutively expressed in ectoderm-derived appendages and is inducibly expressed in the epidermis upon...
The type I intermediate filament keratin 16 (K16) is constitutively expressed in ectoderm-derived appendages and is inducibly expressed in the epidermis upon barrier-compromising challenges. Dominantly acting missense alleles in KRT16 are causative for pachyonychia congenita (PC), a genodermatosis involving debilitating palmoplantar keratoderma (PPK), nail dystrophy, oral lesions and, frequently, alterations in glands and hair. C57Bl/6;Krt16 mice develop oral lesions early after birth and PC-like PPK lesions as young adults. These PPK lesions have a marked dysregulation of skin barrier-related genes and innate immunity effectors (eg danger-associated molecular patterns) and are preceded by oxidative stress secondary to hypoactive Nrf2 signalling. These molecular features are present in PPK lesions of PC patients. Here, we report that all components of the C57Bl/6;Krt16 mouse phenotype occur as well in the FVB strain background, albeit less severely so, a significant observation in the light of variations in the clinical presentation of individuals harbouring disease-causing mutations in the KRT16 gene.
Topics: Alarmins; Alleles; Animals; CD11b Antigen; Carcinogenesis; Female; Filaggrin Proteins; Histones; Human papillomavirus 16; Intermediate Filament Proteins; Keratin-16; Keratoderma, Palmoplantar; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Papillomavirus Infections; Phenotype; Phosphorylation; RNA, Messenger; Sex Factors; Skin Neoplasms
PubMed: 29406601
DOI: 10.1111/exd.13509 -
Indian Journal of Dermatology 2016
PubMed: 27904190
DOI: 10.4103/0019-5154.193686 -
The Journal of Investigative Dermatology May 2018Pachyonychia congenita is an incurable and often debilitating genodermatosis. Topical application of the antioxidative response inducer sulforaphane, however, alleviates...
Pachyonychia congenita is an incurable and often debilitating genodermatosis. Topical application of the antioxidative response inducer sulforaphane, however, alleviates disease symptoms in a murine pachyonychia congenita model, forecasting clinical benefits. The Coulombe laboratory now reports sex-dependent differences in sulforaphane responsiveness of pachyonychia congenita mice, thereby dampening treatment expectations but also unveiling novel aspects of sex-specific oxidative stress reactivity in the epidermis.
Topics: Animals; Epidermis; Female; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Pachyonychia Congenita; Sex Characteristics
PubMed: 29681388
DOI: 10.1016/j.jid.2017.12.017 -
The Pan African Medical Journal 2016Pachyonychia congenita (PC) is a rare hereditary disease, mainly characterized by a painful palmoplantar keratoderma, thickened nails, cysts and white lesions of the...
Pachyonychia congenita (PC) is a rare hereditary disease, mainly characterized by a painful palmoplantar keratoderma, thickened nails, cysts and white lesions of the oral mucosa. Its clinical manifestations are very variable, it may appear from birth to adulthood. This study report the case of a child with pachyonychia congenita associated with bronchiectasis and renal artery stenosis. The diagnosis of pachyonychia congenita was retained based on clinical and histological data. However the presence of renal artery stenosis and bronchiectasis suggests a possible association as part of a particular syndromic group.
Topics: Bronchiectasis; Child; Female; Humans; Pachyonychia Congenita; Renal Artery Obstruction; Syndrome
PubMed: 27795780
DOI: 10.11604/pamj.2016.24.183.9284 -
Heliyon Mar 2024Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and...
Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and cutaneous cysts. And fissured tongue is rarely reported in patients with pachyonychia congenita. The disease is primarily associated with mutations in five keratin genes, namely , , , or . Herein we report a 9-year-old Chinese girl who has thickened nails, keratinized plaques, and fissured tongue since birth. To investigate the underlying genetic cause, whole-exome sequencing and Sanger sequencing were performed in this patient and her family members. We identified a candidate variant c.1460-2_1460del (p.S487Lfs*21) in the gene (NM_005554.4) by whole-exome sequencing. Sanger sequencing revealed the absence of the mutation in both parents, indicating that it is a de novo variant. Thus, the novel heterozygous frameshift mutation c.1460-2_1460del (p.S487Lfs*21) within exon 9 of was identified as the genetic cause of the patient. Our study identified a rare de novo heterozygous frameshift mutation in the gene in a patient with pachyonychia congenita presenting fissured tongue. Our findings expand the gene mutation spectrum of Pachyonychia congenita, and will contribute to the future genetic counseling and gene therapy for this disease.
PubMed: 38468954
DOI: 10.1016/j.heliyon.2024.e27195 -
Human Molecular Genetics Jul 2019The type I intermediate filament keratin 16 (KRT16 gene; K16 protein) is constitutively expressed in ectoderm-derived appendages and in palmar/plantar epidermis and is...
The type I intermediate filament keratin 16 (KRT16 gene; K16 protein) is constitutively expressed in ectoderm-derived appendages and in palmar/plantar epidermis and is robustly induced when the epidermis experiences chemical, mechanical or environmental stress. Missense mutations at the KRT16 locus can cause pachyonychia congenita (PC, OMIM:167200) or focal non-epidermolytic palmoplantar keratoderma (FNEPPK, OMIM:613000), which each entail painful calluses on palmar and plantar skin. Krt16-null mice develop footpad lesions that mimic PC-associated PPK, providing an opportunity to decipher its pathophysiology, and develop therapies. We report on insight gained from a genome-wide analysis of gene expression in PPK-like lesions of Krt16-null mice. Comparison of this data set with publicly available microarray data of PPK lesions from individuals with PC revealed significant synergies in gene expression profiles. Keratin 9 (Krt9/K9), the most robustly expressed gene in differentiating volar keratinocytes, is markedly downregulated in Krt16-null paw skin, well-ahead of lesion onset, and is paralleled by pleiotropic defects in terminal differentiation. Effective prevention of PPK-like lesions in Krt16-null paw skin (via topical delivery of the Nrf2 inducer sulforaphane) involves the stimulation of Krt9 expression. These findings highlight a role for defective terminal differentiation and loss of Krt9/K9 expression as additional drivers of PC-associated PPK and highlight restoration of KRT9 expression as a worthy target for therapy. Further, we report on the novel observation that keratin 16 can localize to the nucleus of epithelial cells, implying a potential nuclear function that may be relevant to PC and FNEPPK.
Topics: Animals; Cell Differentiation; Dermis; HeLa Cells; Humans; Interleukin-1; Isothiocyanates; Kelch-Like ECH-Associated Protein 1; Keratin-16; Keratin-9; Keratinocytes; Keratins; Keratoderma, Palmoplantar; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; Mutation, Missense; NF-E2-Related Factor 2; Signal Transduction; Sulfoxides; Tissue Array Analysis
PubMed: 31220272
DOI: 10.1093/hmg/ddz050 -
Indian Journal of Dermatology 2016The case of an 8-year-old boy is hereby reported, who presented with nail dystrophy, subungual hyperkeratosis, oral leukokeratosis, and numerous follicular papules all...
The case of an 8-year-old boy is hereby reported, who presented with nail dystrophy, subungual hyperkeratosis, oral leukokeratosis, and numerous follicular papules all over the body. The features were consistent with a diagnosis of pachyonychia congenita type 1. The case is being reported for its rarity. We also discuss in a nutshell, the literature till date.
PubMed: 27057022
DOI: 10.4103/0019-5154.177761