A novel KIT missense mutation in one Chinese family with piebaldism

Xian, Yin; Ren, Yun; Yang, Sen; Xu, Sheng Xin; Zhou, Fu Sheng; Du, Weidong; Lin, Da; Wang, Pei Guang; Zhang, Shu Mei; Zhang, Xue Jun

doi:10.1007/s00403-009-0955-5

Cited by 7 publications

(6 citation statements)

References 12 publications

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“…Consistent findings were reported by Krüger et al, who found that the allele frequency of the KIT variant M541L was as high as 8.1% in the healthy population, not differing from chronic myelogenous patients (8.3%) [13]. The V530I variant has to our knowledge, never been described so far, in either AF or other KIT-related diseases such as mastocytosis, GISTs or piebaldism, [14, 15]. The exon 10 V530I substitution alters the transmembrane domain of KIT (contained between amino acids 521–543), and was described in acute myelogenous leukemia [16, 17].…”

Section: Discussionsupporting

confidence: 80%

A V530I Mutation in c-KIT Exon 10 Is Associated to Imatinib Response in Extraabdominal Aggressive Fibromatosis

Kurtz

Asmane

Voegeli

et al. 2010

Sarcoma

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Aggressive fibromatosis (AF) or desmoid tumor is a rare condition, characterized by deep tissue invasion by a monoclonal fibroblastic neoplasm, developed from musculoaponeurotic structures. Surgery is the treatment of choice, but negative margins can hardly been achieved in large tumors, and can lead to major functional disability. AF medical therapy includes nonsteroids anti-inflammatory drugs, tamoxifen, with inconsistent results. Several reports of imatinib efficacy in AF appear in the literature. Here, we describe for the first time a V530I KIT exon 10 mutant that was associated to a dramatic imatinib response in an extraabdominal aggressive fibromatosis. The previously discovered V530I substitution was characterized in the core binding factor AML, but had never been reported in any other condition, so far. In this paper, we discuss the KIT exon 10 mutations or polymorphisms that have been described in a variety of KIT-related conditions, including acute myelogenous leukemia, mastocytosis, and aggressive fibromatosis.

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Section: Discussionsupporting

confidence: 80%

A V530I Mutation in c-KIT Exon 10 Is Associated to Imatinib Response in Extraabdominal Aggressive Fibromatosis

Kurtz

Asmane

Voegeli

et al. 2010

Sarcoma

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“…Therefore, a severe phenotype showing larger leukoderma is associated with severely damaged migration in embryo. After identification of a missense mutation in the KIT gene on the chromosome 4q12 in a large family, 3 32 missense mutations, 3,29,31–47 17 deletions, 31,34,40,41,43,48–54 four insertions, 31,34,35,43 seven nucleotide splice‐site mutations, 31,34,39,41,43 two nonsense mutations 39,41 and one pericentric chromosomal inversion 55 have been identified in the KIT gene or in the chromosomal region of the KIT gene. These genetic studies indicate that the clinical features and phenotypic severity of piebaldism clearly correlate with the site and the type of mutation in the KIT gene 56 …”

Section: Piebaldismmentioning

confidence: 99%

Piebaldism

Oiso

Fukai

Kawada

et al. 2012

The Journal of Dermatology

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Piebaldism is an uncommon autosomal dominantly inherited pigment anomaly characterized by a congenital white forelock and leukoderma on the frontal scalp, forehead, ventral trunk and extremities. It is caused by a loss-of-function mutation in the KIT gene. Genetic analyses reveal a consistent genotype-phenotype relationship in piebaldism. However, recently reported cases of piebaldism that are milder or severer than genetically expected indicate that other factors, such as a modifier gene of MC1R, influence skin and hair color. The KIT ligand ⁄ KIT that triggers the Ras ⁄ mitogenactivated protein kinase signaling pathway play essential functions in the migration, proliferation, survival, melanogenesis and melanosome transfer of the melanocytes. We summarize current research progress in piebaldism and related disorders.

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“…age=markerDetail&key=10603, MGI_4.21). While these mutant sites are mostly located in the intracellular part, except for nonsense mutations, little is known of the extracellular site mutations [5]. Kit W-2Bao mutant is the only known mutant that is located in the extracellular 4th IG-like domain.…”

Section: Structure and Function Of The C-kit Proteinmentioning

confidence: 99%

“…A homologous gene mouse mutation model would be extremely valuable for exploring the mechanisms and therapeutic approaches of Kit related diseases [4][5][6][7].…”

mentioning

confidence: 99%

Abnormal gonad development in Kit W-2Bao mice caused by a Kit gene missense mutation

Liu

et al. 2010

Chin. Sci. Bull.

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Kit W-2Bao mice are single-gene autosomal dominant mutation mice with a B6 background that were bred in our laboratory. Heterozygotes had morphological characteristics including albinism of the abdomen, extremities, and tail, whereas the homozygotes had albinism of the body, black eyes, and infertility. The homozygous mutants showed small, structurally abnormal gonads, and lacked germ cells. Heterozygous male mice lacked germ cells in some contorted seminiferous tubules. This mutation has been mapped at 43.8 cM from the centromere in chromosome 5 by linkage analysis and Kit has been identified as the candidate gene. After Kit full-length mRNA amplification, it was found that a G to T conversion at position 1228 in the ORF changed the 410th amino acid from V to F. This amino acid change could affect the protein's secondary structure. Heterozygous mutant mice were intercrossed and homozygous mutant mice were bred and genotyped. We found that no primordial germ cells (PGCs) appeared in the urogenital ridge area at fetus day 11.5 in the homozygotes. The number of PGCs also significantly decreased in heterozygotes. At fetus day 15.5, the differentiation of the testis tubule structure was unclear; as well, they contained no spermatogonia. Female homozygotes contained no primordial follicles in the ovary. The numbers of PGCs and primordial follicles were significantly decreased in heterozygous mice. W -2Bao is the only mutated site in the extracellular 4th Ig-like domain and this mutant mouse model provides new material for the study of the mechanism of reproductive system development. mouse, Kit, missense mutation, gonad Citation: Wu B J, Yin L J, Lu Z L, et al. Abnormal gonad development in Kit W-2Bao mice caused by a Kit gene missense mutation.

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A novel KIT missense mutation in one Chinese family with piebaldism

Cited by 7 publications

References 12 publications

A V530I Mutation in c-KIT Exon 10 Is Associated to Imatinib Response in Extraabdominal Aggressive Fibromatosis

A V530I Mutation in c-KIT Exon 10 Is Associated to Imatinib Response in Extraabdominal Aggressive Fibromatosis

Piebaldism

Abnormal gonad development in Kit W-2Bao mice caused by a Kit gene missense mutation

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