■KIT是一种参与增殖的原癌基因,生存,和调节黑素细胞,肥大细胞,和Cajal的间质细胞.据报道,KIT的突变与色素沉着过度和扁豆有关,肥大细胞增多症,和胃肠道间质瘤(GIST)。据报道,KIT的一些热点突变与肥大细胞增多症和GIST有关,而KIT突变与色素沉着过度和扁桃体之间的关系尚未完全阐明。
■在这项研究中,我们提出了一个三代中国家系,其进行性色素沉着过度,并以常染色体显性遗传方式遗传。进行高通量测序以捕获先证者的外周血样品中的遗传变异。此外,进行Sanger测序以进一步验证结果。我们还回顾了先前关于色素沉着过度和lentigines的KIT突变的文献。
■确定了KIT基因的错义突变:c。2485G>C,这是在先证者和他被侮辱的父亲中共同隔离的。生殖系KIT突变表现为全身性色素沉着过度和扁桃体而无全身性疾病是罕见的。在以往的文献中,只有2例报道了与该表型相关的c.2485G>C突变。
■我们的血统,加上这两份报告,表明该种系KIT突变可能存在表型-基因型相关性,这可能对遗传咨询有帮助,KIT的进一步功能分离,以及未来靶向治疗的设计。
UNASSIGNED: KIT is a proto-oncogene that is involved in the proliferation, survival, and regulation of melanocytes, mast cells, and the interstitial cells of Cajal. Mutations of KIT have been reported to be associated with hyperpigmentation and lentigines, mastocytosis, and gastrointestinal stromal tumors (GISTs). Some hotspot mutations of KIT have been reported to be associated with mastocytosis and GISTs, while the relationship between KIT mutations and hyperpigmentation and lentigines has not been fully elucidated.
UNASSIGNED: In this study, we presented a three-generation Chinese pedigree with progressive hyperpigmentation and generalized lentigines inherited in an autosomal dominant pattern. High-throughput sequencing was performed to capture genetic variations in peripheral blood samples of the proband. Also, Sanger sequencing was performed to further verify the result. We also reviewed previous literature on
KIT mutations with hyperpigmentation and lentigines.
UNASSIGNED: A missense mutation of the KIT gene was identified: c. 2485G > C, which was co-segregated in the proband and his insulted father. Germline KIT mutations presenting as generalized hyperpigmentation and lentigines without systemic disorders are rare, with only two
reports of c. 2485G > C mutation associated with this phenotype in previous literature.
UNASSIGNED: Our pedigree, together with those two
reports, indicates a possible phenotype-genotype correlation of this germline KIT mutation, which might be helpful for genetic counseling, further functional segregation of
KIT, and design of targeted therapy in the future.