斑驳病患者KIT基因突变的检测

目的:研究斑驳病患者中KIT基因突变,为该病的基因诊断及治疗奠定基础。方法:调查2个斑驳病家系,其中家系1共有10名成员,4人为斑驳病患者;家系2共有8名成员,3人为斑驳病患者。对患者及其家系中健康人的KIT基因进行测序,并选择同时期100例来本院进行健康体检的志愿者进行对照分析。结果:患者均表现为先天性白斑和白色额发,且白斑数目随年龄增长而增加,白斑形状从开始时的三角形或棱形逐渐融合成大片,分布从开始时的前额逐渐分布至四肢、关节、躯干,白斑面积达体表总面积60%以上。测序结果表明,两个家系中7例患者存在同样的突变,即KIT基因的第12位外显子中的第1 861位碱基发生改变,从鸟嘌呤(G)突变成腺嘌呤(A),导致621位氨基酸残基从缬氨酸变成了苏氨酸,而家系中健康人及对照组在此位点不存在该基因突变。扩增21个外显子,全部扩增成功,其他外显子未发现突变情况。结论:斑驳病患者中存在KIT基因突变。     

斑驳病的临床表型与KIT基因突变位点相关性及治疗的研究进展

斑驳病是一种少见的先天性常染色体显性遗传性疾病.其显著的临床特征是额前中线见三角形或钻石形白发及白斑.白斑内黑素细胞缺失.目前研究表明,胚胎发育时黑素细胞迁移、繁殖障碍与基因突变相关,KIT基因突变是斑驳病的致病基因,KIT基因突变引起斑驳病的临床表型轻重有很大差异.概述KIT基因突变的位点与临床表型轻重的关系.     

斑驳病一家系

斑驳病是一种罕见的常染色体显性遗传病。临床典型特征是先天性白发和白斑。先证者女,2岁3个月,额、腹及双下肢白斑和白色额发2年余。其父亲亦有白色额发和白斑,家族成员共3代19人,患病6人,年龄最小2岁,最大72岁。每代均有成员发病,男3例,女3例,符合常染色体显性遗传。     

斑驳病致病基因的研究进展

斑驳病是一种较少见的由黑素细胞发育不良引起的常染色体显性遗传病,典型临床特征是先天性额部中央呈三角形或菱形的白斑和白发.该病具有遗传异质性,大多数斑驳病由kit基因突变引起.遗传分析揭示,kit基因突变点与临床表型关系密切,少数报告表明,可能存在其他因素引起基因型与表型不一致,有学者对该病的常染色体显性遗传特点提出质疑.kit基因编码蛋白属Ⅲ型酪氨酸激酶受体,kit基因突变导致受体酪氨酸激酶功能下降或失活,信号传导功能受损,成黑素细胞在胚胎发育期的增殖和迁移发生障碍,从而导致斑驳病的发生.     

斑驳病一家系报告

先证者男,4个半月。出生时前头部、额部、腹部及双大腿下1/2、双小腿上2/3与左肘部即被发现有白斑,头部白斑处可见白发。其家系中四代42人中有8人发病,男3例,女5例。     

斑驳病一家系分析

目的探讨斑驳病的病因及临床表现。方法对斑驳病一家系进行调查分析。结果一家系5代18人中有10人发病,其中男6例,女4例。该家系临床表现均为先天性腹部和双下肢不规则白斑,4例有额部三角形白发。结论斑驳病是肥大细胞/干细胞生长因子受体(ckit)基因突变引起的基因病。当ckit基因功能发生变化时,黑素母细胞的增殖和迁移在胚胎发育期间发生障碍,在其到达皮肤表皮某部位前发生停止导致疾病发生。斑驳病临床表现的轻重与ckit基因突变的不同位点密切相关。     

斑驳病的分子遗传学研究进展

斑驳病是一种少见的先天性常染色体显性遗传性疾病。该病具有遗传异质性,主要由位于4q12上的KIT基因突变引起,突变位点与临床表型密切相关,部分病例由SLUG基因缺失所致。SCF/KIT信号传导途径对黑素细胞的存活、迁移、增殖和分化具有重要调控作用。小鼠模型为研究人类斑驳病提供重要依据。     

kit基因c.2472+1G＞A突变在一个中国家系导致斑驳病

目的 对一斑驳病家系行分子遗传学分析,明确该家系的致病突变.方法 运用PCR、逆转录PCR和DNA测序对家系成员kit基因进行基因检测.结果 先证者的kit基因存在c.2472+1G>A的杂合突变,该突变使第17号外显子3'端剪接位点丢失,导致kit基因所编码的mRNA第17号外显子缺失,家系中其他患者均存在相同突变,家系中正常个体中没有此突变.结论 kit基因的c.2472+1G>A杂合突变是导致家系成员发生斑驳病的致病突变.     

斑驳病一家系报道

斑驳病也称图案状白皮病，少见，为常染色体湿性遗传病，累及黑素母细胞的分化，本文报道一斑驳病家系。     

斑驳病c-kit基因突变检测

目的：检测2例散发斑驳病患儿及其父母c-kit基因的突变情况。方法：收集2例斑驳病患儿及其父母的临床资料,提取其外周血DNA,采用PCR扩增c-kit基因编码区的全部外显子,DNA直接测序,明确突变位点。针对所发现的突变位点以TaqⅠ酶及SmaⅠ酶进行限制性内切酶检测。结果：2例患儿c-kit基因分别于第1862位C→A及第1784位T→C,使密码子GCT→GAT和CTG→CCG,导致Ala621Asp及Leu595Pro突变。2例患儿父母以及50名健康对照者不存在此两种基因突变。结论：Ala621Asp及Leu595Pro均为新生（denovo）突变,此突变是2例散发斑驳病患儿的主要病因。     

A novel KIT missense mutation in one Chinese family with piebaldism

Piebaldism is an autosomal dominant disorder characterized by congenital leukoderma, mostly affecting forehead, abdomen and knee. Previous studies have revealed that piebaldism is caused by mutations of the KIT gene, which encodes the cell surface transmembrane tyrosine kinase receptor for KIT ligand. We reported here a Chinese Han family with piebaldism, and performed mutation detection of KIT gene by direct sequencing. A novel missense mutation C58G was identified in the patients, but not in the healthy individuals from the family and 100 unrelated controls. This study contributes to the database on KIT in piebaldism and enriches the knowledge about the genotype/phenotype correlation.     

A novel missense mutation of CYLD gene in a Chinese family with multiple familial trichoepithelioma

Multiple familial trichoepithelioma (MFT, OMIM 601606) is an autosomal dominantly inherited disease. It is characterized by numerous skin-colored papules on the central face. Pathogenic mutations in the CYLD gene have been identified. In this report, we identified a novel mutation of CYLD gene in a Chinese family with MFT. It is a novel heterozygous nucleotide G→A transition at position 2,317 in exon 17 of the CYLD gene. Our study expands the database on the CYLD gene mutations in MFT.     

A novel missense mutation of KRT2 gene in a family with ichthyosis bullosa of Siemens

目的:检测1个Siemens大疱性鱼鳞病家系KRT2基因突变,并总结国内外相关文献.方法:提取先证者及其亲属共4人外周血DNA,对KRT2基因的全部9个外显子和侧翼序列进行PCR扩增和测序,并以150名无关系正常人作为对照.结果:先证者KRT2基因外显子第568位碱基发生G→C杂合突变(c.G568C),可导致其编码的第190位氨基酸由丙氨酸变成脯氨酸(p.A190P),该突变位点在家族患者中呈现疾病共分离现象,150名无关系正常人未检测到该突变.结论:KRT2基因的p.A190P突变可能为该家系Siemens大疱性鱼鳞病的发病原因,这个位点在国内外均属首次报道的新突变位点.     

A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome

Brooke-Spiegler syndrome (BSS, familial cylindromatosis or turban tumor syndrome) is an inherited disease characterized by neoplasms of the skin appendages such as cylindroma, trichoepithelioma, and spiradenoma. The disease has been mapped to 16q12-13, and mutations in the CYLD gene have been identified in families with this disorder. Of interest, multiple familial trichoepithelioma (MFT) has been described as a distinct disorder characterized by the familial occurrence of trichoepitheliomas. MFT has been mapped to 9p21; however, to date a candidate gene has not been identified. In this report, we describe a four-generation family with BSS presenting predominantly with trichoepitheliomas (resembling MFT phenotype). We identified a novel missense mutation in the CYLD gene, designated E474G, in the affected individuals of this family. Our findings exemplify clinical heterogeneity within BSS and extend the body of evidence that mutations in CYLD are implicated in this disease. Although not conclusive, these findings suggest that BSS and MFT may represent a single entity.