Case of Kindler syndrome resulting from mutation in the <i>FERMT1</i> gene

Wada, Makoto; Masuda, Koji; Tsuruta, Daisuke; Tamai, Katsuto; Lai-Cheong, Joey; McGrath, John A.; Katoh, Norito

doi:10.1111/j.1346-8138.2012.01598.x

Cited by 8 publications

(12 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KIND1 loss-of-function mutation is linked to Kindler syndrome (KS, OMIM173650), an autosomal recessive disorder characterized by skin fragility with progressive atrophy, poikiloderma, photosensitivity and chronic mucosal inflammation (Has et al, 2011). KS-driver mutations (>70) consist of deletions, insertions, nonsense, splice-site and missense mutations that result in expression of a nonfunctional mutant KIND1 or at a reduced level (Arita et al, 2007, Fuchs-Telem et al, 2014, Has, Castiglia, 2011, Has et al, 2015, Lai-Cheong et al, 2009, Sadler et al, 2006, Wada et al, 2012). In addition to skin fragility, KS keratinocytes display premature senescence (Piccinni et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

KIND1 Loss Sensitizes Keratinocytes to UV-Induced Inflammatory Response and DNA Damage

Luo

Zhang

et al. 2017

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Loss-of-function of KIND1, a cytoskeletal protein involved in β1-integrin function, causes Kindler Syndrome (KS), a genetic disease characterized by skin fragility, photosensitivity and increased risk of squamous cell carcinoma (SCC). Dysregulation of β1-integrin underlies KS skin fragility. However, the mechanisms underlying SCC susceptibility are unclear. Here, we demonstrate that gene silencing of KIND1 decreased keratinocyte proliferation and increased apoptosis in vitro and in skin grafts regenerated on mice, which was correlated with reduced cyclinB1. In addition, KIND1-loss sensitized keratinocytes to cytokine and UV-induced NF-κB and JNK activation and upregulation of CXCL10 and TNFα. Moreover, KIND1-loss impaired DNA-repair, as indicated by the increased detection of γH2AX and cyclobutane pyrimidine dimers (CPD) 24 hours post UVB-radiation. Genetic or pharmacological JNK-inhibition and NF-κB-inhibition markedly reduced CPD-positive cells. Further, we show that KIND1 was regulated by JunB at the transcriptional level and, like JunB, it was downregulated in human SCC cells. Together, these results indicate that KIND1 is important not only for keratinocyte proliferation but also for the suppression of UV-induced inflammation and DNA-damage. These latter findings support a tumor suppressor function for KIND1, and identified JNK and NF-κB as potential therapeutic targets for prevention of SCC in KS patients.

show abstract

Section: Introductionmentioning

confidence: 99%

KIND1 Loss Sensitizes Keratinocytes to UV-Induced Inflammatory Response and DNA Damage

Luo

Zhang

et al. 2017

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…Certain mutations occurred in the same population in different reports, indicating population-specific pathogenic mutations. For instance, c.1089delG (38)(39)(40) was reported three times in only Japanese patients and c.1848_1851dupGGAA (9,10,41) was reported three times in only Turkish patients. Further genotype-phenotype correlation studies are required to clarify these associations.…”

Section: Discussionmentioning

confidence: 99%

A novel frameshift mutation in the <em>FERMT1</em> gene in a Chinese patient with Kindler syndrome

Yang

et al. 2020

Exp Ther Med

View full text Add to dashboard Cite

Kindler syndrome (KS) is a rare subtype of epidermolysis bullosa that is inherited in an autosomal recessive manner with mutations in FERMT1. A number of mutations in FERMT1 have been identified in KS. The current study reported a 33-year-old Chinese man who exhibited a wide variety of clinical features, including formation of blisters, photosensitivity, cutaneous atrophy and poikiloderma, telangiectasia of the face and neck, contracture of the end limbs, nail dystrophy, muscle, eye and oral damage, tympanitis, esophagus narrowing, pneumothorax and palmoplantar keratoderma. The patient's parents were healthy and the patient had no siblings or children. Peripheral blood was obtained from the patient, his parents and 100 controls, who were admitted to the Dermatology Clinic of Shanghai Skin Disease Hospital, Shanghai, China. A multi-gene panel test consisting of 541 genetic loci of monogenic hereditary diseases was performed. The results identified one novel homogenous mutation in the patient: c.1885_1901del (p.Val629fs) on exon 15 in FERMT1. The patient's parents exhibited heterogeneous identical mutations. This mutation was absent in the control group. The results of the multi-gene panel test were further verified by Sanger sequencing. Based on the clinical manifestations and genetic analysis, KS was diagnosed in the patient. The current study reported a Chinese case of KS with one novel mutation c.1885_1901del in FERMT1 and presented a brief summary of all pathogenic mutations in FERMT1 that have been reported in KS between 1984 and May 2020 via a PubMed literature search.

show abstract

“…Perioral areas can present with erosions, crusts, and chronic cheilitis. 132,133,135,138,[155][156][157][158][159][160][161][162][163][164] Glandular cheilitis of the lower lip have been reported in a 7-year-old patient. 159…”

Section: Peri-oral Tissue Involvementmentioning

confidence: 99%

“…Partial obliteration of the oral vestibule, also described as: "synechiae between the lips and the gums," "adhesions between the lips and gingiva," or "atrophy of the buccal mucosa" has been described in several patients with KEB (Image 2.20). 4,132,133,138,155,161,166,167,[169][170][171][172][181][182][183] Reticular pigmentation on the cheek, 160,163 white hyperkeratotic papules on the buccal mucosa, 165…”

Section: Oral Vestibule Obliterationmentioning

confidence: 99%

Clinical practice guidelines: Oral health care for children and adults living with epidermolysis bullosa

Krämer

Lucas

Gamboa

et al. 2020

Special Care in Dentistry

View full text Add to dashboard Cite

Background: Inherited epidermolysis bullosa (EB) is a genetic disorder characterized by skin fragility and unique oral features. Aims: To provide (a) a complete review of the oral manifestations in those living with each type of inherited EB, (b) the current best practices for managing oral health care of people living with EB, (c) the current best practices on dental implant-based oral rehabilitation for patients with recessive dystrophic EB (RDEB), and (d) the current best practice for managing local anesthesia, This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

show abstract

Case of Kindler syndrome resulting from mutation in the FERMT1 gene

Cited by 8 publications

References 5 publications

KIND1 Loss Sensitizes Keratinocytes to UV-Induced Inflammatory Response and DNA Damage

KIND1 Loss Sensitizes Keratinocytes to UV-Induced Inflammatory Response and DNA Damage

A novel frameshift mutation in the <em>FERMT1</em> gene in a Chinese patient with Kindler syndrome

Clinical practice guidelines: Oral health care for children and adults living with epidermolysis bullosa

Contact Info

Product

Resources

About