CAJ | 학술논문

通过对国人Ⅰ型遗传性淋巴水肿一家系分子遗传学检测,报告VEGFR-3基因新突变.首先在Ⅰ型遗传性淋巴水肿对该家系进行致病基因的连锁分析,然后用DNA直接测序方法进行基因突变分析.连锁分析和单倍体分析确定该家系致病基因位于5q35.3,与Ⅰ型遗传性淋巴水肿连锁.VEGFR-3基因突变分析发现了一个新的错义突变D1055V.该错义突变在家系中共分离,且在100个正常对照组中未发现该序列改变.本研究首次报告了国内Ⅰ型遗传性淋巴水肿VEGFR-3基因新的错义突变D1055V,丰富了VEGFR-3基因基因突变谱,为今后开展遗传性淋巴水肿的基因诊断和遗传咨询奠定基础.
통과대국인Ⅰ형유전성림파수종일가계분자유전학검측,보고VEGFR-3기인신돌변.수선재Ⅰ형유전성림파수종대해가계진행치병기인적련쇄분석,연후용DNA직접측서방법진행기인돌변분석.련쇄분석화단배체분석학정해가계치병기인위우5q35.3,여Ⅰ형유전성림파수종련쇄.VEGFR-3기인돌변분석발현료일개신적착의돌변D1055V.해착의돌변재가계중공분리,차재100개정상대조조중미발현해서렬개변.본연구수차보고료국내Ⅰ형유전성림파수종VEGFR-3기인신적착의돌변D1055V,봉부료VEGFR-3기인기인돌변보,위금후개전유전성림파수종적기인진단화유전자순전정기출.
A novel mutation of vascular endothelial growth factor receptor gene (VEGFR-3), was identified in a four-generation Chinese family with hereditary lymphedema type Ⅰ (HL-Ⅰ). Genetic linkage analysis was performed on the known genetic locus for HL-Ⅰ with a panel of polymorphic markers, and then mutations were screened out by direct sequencing. By genotyping, the family showed the linkage to HL-Ⅰ locus on 5q35.3. Mutation screening analysis of the exons encoding the intracellular kinase domains of VEGFR-3, revealed a novel missense mutation D1055V. This mutation cosegregated with the disease phenotype in the family and was not found in 100 normal controls. This finding has expanded the spectrum of the VEGFR-3 gene mutations causing HL-Ⅰ, and will be useful for further genetic consultation and genetic diagnosis.