Journal Article10.1111/PDE.13040
Familial Progressive Hyperpigmentation, Cutaneous Mastocytosis, and Gastrointestinal Stromal Tumor as Clinical Manifestations of Mutations in the c-KIT Receptor Gene.
Tatiana Piqueres-Zubiaurre,Zuriñe Martínez de Lagrán,Ricardo González-Pérez,Amaia Urtaran-Ibarzabal,Guiomar Perez de Nanclares +4 more
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TL;DR: Familial progressive hyperpigmentation (FPH) is an autosomal dominant disorder characterized by the appearance ofhyperpigmented patches on the skin from early infancy that increase in size and number with age.
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Abstract: Background Familial progressive hyperpigmentation (FPH) is an autosomal dominant disorder characterized by the appearance of hyperpigmented patches on the skin from early infancy that increase in size and number with age. Methods We report the clinical and molecular studies of an 11-year-old boy who had areas of hyperpigmentation since birth that had spread across his body as irregular hyperpigmented macules and papules, and include relevant history in family members. Results Affected members of his family shared a mutation in the c-KIT gene. All had progressive hyperpigmentation, in some cases accompanied by gastrointestinal stromal tumors and mastocytoma. There have been few reports of familial progressive hyperpigmentation together with systemic manifestations. Conclusions Molecular analysis of c-KIT should be considered in the presence of FPH with systemic involvement.
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Citations
Remarkable effects of imatinib in a family with young onset gastrointestinal stromal tumors and cutaneous hyperpigmentation associated with a germline KIT-Trp557Arg mutation: case report and literature overview
Sheima Farag,L. E. van der Kolk,H. van Boven,A.C.J. van Akkooi,Geerard L. Beets,J. W. Wilmink,Neeltje Steeghs +6 more
TL;DR: Imatinib treatment in GIST patients harboring a germline KIT mutation shows favorable and long-term responses in both the tumor and the phenotypical hyperpigmentation.
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Autosomal dominant progressive hyperpigmentation and lentigines in a Japanese pedigree due to a missense mutation near the C-terminus of KIT.
TL;DR: Ten cases of hyperpigmentation and 2 cases of lentigines were reported in familial mastocytosis or GIST associated with germline KIT mutations, and the binding of KITLG to KIT regulates the migration, proliferation, differentiation and survival of melanocytes, and regulates melanogenesis and melanosome transfer.
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Novel KIT mutation presenting as marked lentiginosis
Alain K Tran,Annette Pearce,Marcos López-Sánchez,Luis A. Pérez-Jurado,Luis A. Pérez-Jurado,Luis A. Pérez-Jurado,Christopher Barnett +6 more
TL;DR: The case of a 6‐year‐old girl who presented with atypical lentiginosis and hyperpigmentation caused by a de novo genetic variant in the KIT gene is reported.
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Familial progressive hyperpigmentation: A family resurvey and ultrastructural skin investigation.
TL;DR: Electron microscopic examination of skin from the proband of the Chinese FPH family showed that there were more melanosomes in lesional keratinocytes than in perilesional Keratinocytes, and a large number of nonmembrane‐bound melanosome complexes were observed in the keratinocyte of hyperpigmented areas.
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KIT and Other Mutations in Mastocytosis
Siham Bibi,Michel Arock +1 more
- 01 Jan 2020
TL;DR: In advanced SM patients, additional oncogenic lesions, including RAS, TET2, SRSF2, ASXL1, CBL, and/or RUNX1 mutations, have been recently described and may accumulate, thus worsening the prognosis and frequently a multi-mutated disease for which KIT-targeted drugs might probably not be sufficient for a permanent cure.
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References
Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy.
TL;DR: Different types of activating mutations respond differentially to KIT inhibitors, so classification of individuals on the basis of specific mutations is necessary to guide therapy.
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Gastrointestinal stromal tumors (GIST): C-kit mutations, CD117 expression, differential diagnosis and targeted cancer therapy with Imatinib.
TL;DR: Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract as mentioned in this paper.
Gain-of-Function Mutation of KIT Ligand on Melanin Synthesis Causes Familial Progressive Hyperpigmentation
Zhiqiang Wang,Zhiqiang Wang,Lizhen Si,Lizhen Si,Quan Tang,Quan Tang,Debao Lin,Zhangjie Fu,Zhangjie Fu,Jing Zhang,Jing Zhang,Bin Cui,Bin Cui,Yufei Zhu,Yufei Zhu,Xianghua Kong,Min Deng,Min Deng,Yu Xia,Yu Xia,Heng Xu,Heng Xu,Weidong Le,Weidong Le,Landian Hu,Landian Hu,Xiangyin Kong,Xiangyin Kong +27 more
TL;DR: Data provided the first genetic evidence that the FPH disease is caused by the KITLGN36S mutation, which has a gain-of-function effect on the melanin synthesis and opens a new avenue for exploration of the genetic mechanism of FPH.
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Sequence Analysis of Two Genomic Regions Containing the KIT and the FMS Receptor Tyrosine Kinase Genes
Catherine André,Annie Hampe,Philippe Lachaume,Emmanuel Martin,Xao-Ping Wang,Vladimir Manus,Wei-Xin Hu,Francis Galibert +7 more
TL;DR: Comparison of the two sequences shows that, while introns of both genes have extensively diverged in size and sequence, this divergence is, at least in part, due to intron expansion through internal duplications, as suggested by the discrete extant analogies.
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KITLG Mutations Cause Familial Progressive Hyper- and Hypopigmentation
Mustapha Amyere,Thomas Vogt,Joe Hoo,Flemming Brandrup,Anette Bygum,Laurence M. Boon,Miikka Vikkula +6 more
TL;DR: In aggregate, mutations in a single gene cause various pigmentation disorders: FPH, FPHH, and likely DUH2, and therefore, KITLG is an important modulator of skin pigmentation.
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