Novel and recurrent FERMT1 gene mutations in Kindler syndrome.
Tanasit Techanukul,Gomathy Sethuraman,Abraham Zlotogorski,Liran Horev,Michal Macarov,Alison Trainer,Kenneth Fong,Marko Lens,Ljiljana Medenica,V. Ramesh,John A. McGrath,Joey Lai-Cheong +11 more
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TLDR
Five novel and three recurrent loss-of-function FERMT1 mutations in eight individuals with Kindler syndrome are described, and an overview of genotype-phenotype correlation in this disorder is provided.Abstract:
Kindler syndrome (OMIM 173650) is an autosomal recessive condition characterized by skin blistering, skin atrophy, photosensitivity, colonic inflammation and mucosal stenosis. Fewer than 100 cases have been described in the literature. First reported in 1954, the molecular basis of Kindler syndrome was elucidated in 2003 with the discovery of FERMT1 (KIND1) loss-of-function mutations in affected individuals. The FERMT1 gene encodes kindlin-1 (also known as fermitin family homologue 1), a 77 kDa protein that localizes at focal adhesions, where it plays an important role in integrin signalling. In the current study, we describe five novel and three recurrent loss-of-function FERMT1 mutations in eight individuals with Kindler syndrome, and provide an overview of genotype-phenotype correlation in this disorder.read more
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Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting
Jiansong Huang,Xia Li,Shi Xiaofeng,Mark Zhu,Jinghan Wang,Shujuan Huang,Xin Huang,Huafeng Wang,Ling Li,Huan Deng,Yulan Zhou,Jian-Hua Mao,Zhangbiao Long,Zhixin Ma,Wenle Ye,Jiajia Pan,Xiaodong Xi,Jie Jin +17 more
TL;DR: The bidirectional signal transduction of integrin αIIbβ3 in platelets is described, as well as the proteins responsible for its regulation and therapeutic agents that target integrinαIIb β3 and its signaling pathways.
Journal ArticleDOI
Kindler syndrome: extension of FERMT1 mutational spectrum and natural history.
Cristina Has,Daniele Castiglia,Marcela Del Rio,Marta Garcia Diez,Eugenia Piccinni,Dimitra Kiritsi,Jürgen Kohlhase,Peter Itin,Ludovic Martin,Judith Fischer,Giovanna Zambruno,Leena Bruckner-Tuderman,Leena Bruckner-Tuderman +12 more
TL;DR: Clinical and genetic data are reviewed, and the natural history of the Kindler syndrome is delineated, for example, age at onset of symptoms, or risk of malignancy, to enable the development of prevention strategies for disease complications.
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Whole-exome sequencing improves mutation detection in a diagnostic epidermolysis bullosa laboratory
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TL;DR: Current approaches in EB diagnostics involve skin biopsy for immunohistochemistry and transmission electron microscopy, and Sanger sequencing of candidate genes, and may fail to identify pathogenic mutations in ~15% of cases.
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Identification of Variants in Genes Associated with Single-gene Inflammatory Bowel Disease by Whole-exome Sequencing.
James J. Ashton,Gaia Andreoletti,Tracy Coelho,Tracy Coelho,Rachel Haggarty,Akshay Batra,Nadeem A. Afzal,R Mark Beattie,Sarah Ennis +8 more
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References
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Journal ArticleDOI
Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome
Dawn H. Siegel,G H S Ashton,Homero Penagos,James V. Lee,Heidi S. Feiler,Kirk C. Wilhelmsen,Andrew P. South,Frances J.D. Smith,Alan R. Prescott,V Wessagowit,Noritaka Oyama,Masashi Akiyama,Daifullah Al Aboud,Khalid A Al Aboud,Ahmad Al Githami,Khalid Al Hawsawi,Abla Al Ismaily,Raouf Al-Suwaid,David J. Atherton,Ruggero Caputo,Jo David Fine,Ilona J. Frieden,Elaine Fuchs,Richard M. Haber,Takashi Harada,Yasuo Kitajima,Susan B. Mallory,Hideoki Ogawa,Sedef Şahin,Hiroshi Shimizu,Yasushi Suga,Gianluca Tadini,Kikuo Tsuchiya,Colin Wiebe,Fenella Wojnarowska,Adel B. Zaghloul,Takahiro Hamada,R. Mallipeddi,Robin A.J. Eady,W.H. Irwin McLean,John A. McGrath,Ervin H. Epstein +41 more
TL;DR: Kindler syndrome is, to the authors' knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin- ECM linkage.
Journal ArticleDOI
Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome
Florence Jobard,Bakar Bouadjar,Frédéric Caux,Smail Hadj-Rabia,Christina Has,Fumi Matsuda,Jean Weissenbach,Mark Lathrop,Jean François Prud'homme,Judith Fischer +9 more
TL;DR: Kindler syndrome is a rare autosomal-recessive genodermatosis characterized by bullous poikiloderma with photosensitivity and the localization to chromosome 20p12.3 is reported by homozygosity mapping and the identification of a new gene, which is proposed to name kindlerin, which could be involved in cell adhesion processes via integrin signaling.
Journal ArticleDOI
Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction.
Siegfried Ussar,Markus Moser,Moritz Widmaier,Emanuel Rognoni,Christian Harrer,Orsolya Genzel-Boroviczény,Reinhard Fässler +6 more
TL;DR: It is shown that deleting Kindlin-1 in mice gives rise to skin atrophy and an intestinal epithelial dysfunction with similarities to human UC, which results in perinatal lethality and is triggered by defective intestine epithelial cell integrin activation, leading to detachment of this barrier followed by a destructive inflammatory response.
Journal ArticleDOI
Kindlin-1 is a phosphoprotein involved in regulation of polarity, proliferation, and motility of epidermal keratinocytes.
Corinna Herz,Corinna Herz,Monique Aumailley,Carsten Schulte,Ursula Schlötzer-Schrehardt,Leena Bruckner-Tuderman,Cristina Has +6 more
TL;DR: Results show that kindlin-1 plays a role in keratinocyte adhesion, polarization, proliferation, and migration, and it is involved in organization and anchorage of the actin cytoskeleton to integrin-associated signaling platforms.
Journal ArticleDOI
Kindler syndrome: a focal adhesion genodermatosis
Joey Lai-Cheong,Akio Tanaka,G. Hawche,P. Emanuel,C. Maari,M. Taskesen,S. Akdeniz,Lin Liu,John A. McGrath +8 more
TL;DR: The clinical, cellular and molecular pathology of Kindler syndrome are reviewed, the role of fermitin family homologue 1 in keratinocyte biology is discussed and it is discussed how this protein plays a crucial role in Keratinocyte migration, proliferation and adhesion.
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Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome
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