四个小睑裂综合征家系的FOXL2基因遗传分析  

Genetic analysis of the FOXL2 gene on pedigree with blepharophimosis-ptosis-epicanthus inversus syndrome

作　　者：高明敏 宋宗明 黄俊萍 邢枫 Gao Mingmin;Song Zongming;Huang Junping;Xing Feng(Department of Ocular Plastic and Cosmetic,Henan Provincial People’s Hospital,Henan Eye Hospital&Henan Eye Institute,People’s Hospital of Zhengzhou University,Zhengzhou 450003,China;Department of Retinal Disease,Henan Provincial People’s Hospital,Henan Eye Hospital&Henan Eye Institute,People’s Hospital of Zhengzhou University,Zhengzhou 450003,China;Department of Ocular Trauma,Henan Provincial People’s Hospital,Henan Eye Hospital&Henan Eye Institute,People’s Hospital of Zhengzhou University,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院(郑州大学人民医院)河南省立眼科医院眼整形科,450003 [2]河南省人民医院(郑州大学人民医院)河南省立眼科医院眼底病科,450003 [3]河南省人民医院(郑州大学人民医院)河南省立眼科医院眼外伤科,450003

出　　处：《中华整形外科杂志》2021年第12期1390-1396,共7页Chinese Journal of Plastic Surgery

摘　　要：目的探寻小睑裂综合征(BPES)的FOXL2基因突变情况。方法2018年1月至2021年1月河南省立眼科医院对4个BPES患病家系进行了FOXL2基因检测分析。采用荧光定量PCR、Sanger测序或多重连接探针扩增技术(MLPA)检测先证者和其他家系成员的FOXL2基因突变情况。结果4个家系共有8例BPES患者,男4例,女4例,年龄4~52岁,平均24岁。各家系符合常染色体显性的遗传模式。家系1先证者的FOXL2基因在染色体Chr3∶138,944,224-138,947,137区域存在杂合缺失;家系2先证者的FOXL2基因在5’端上游存在一段杂合性缺失;家系3先证者及患病母亲FOXL2基因存在c.241 T>C(p.Y81 H)的错义突变;家系4的先证者及患病母亲存在c.672_701dup(p.A224_A234dup)重复突变。结论FOXL2基因c.241 T>C(p.Y81 H)和c.672_701dup(p.A224_A234dup)突变为既往已在不同人种中报道的热点突变。FOXL2基因Chr3∶138,944,224-138,947,137区域杂合缺失和5’端上游的杂合缺失为未曾报道的新突变,为遗传咨询和生育指导提供了新依据,丰富了FOXL2基因突变谱。Objective To screen for the mutation types of the FOXL2 in 4 families with blepharophimosis-ptosis-epicanthus inversus syndrome(BPES),and explore their genotype-phenotype correlations.Methods To retrospectively analyze the result of FOXL2 gene detection by fluorescence quantification PCR,Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA)in probands and families of BPES from January 2018 to January 2021,obtain mutation sites of pathogenic genes.Results 4 BPES families(8 cases)including 4 males and 4 females,with age ranged form 4 to 52 years(mean 24).The proband of family 1 has fragment deletion of Chr3∶138,944,224-138,947,137 region of FOXL2 gene.Proband of family 2 has heterozygosity deletion upstream of the 5’end of FOXL2 gene.There are missense mutations of c.241 T>C(p.Y81 H)in proband and affected mother of family 3.There are c.672_701dup(p.A224_A234dup)in-frame duplication mutations in proband and affected mother of family 4.Conclusions Identification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance.The fragment deletion of Chr3∶138,944,224-138,947,137 region of FOXL2 gene and heterozygosity deletion upstream of the 5’end of FOXL2 gene are all new mutations that have not been reported.The novel mutations have enriched the mutation spectrum of the FOXL2 gene.

关 键 词：睑裂狭小 遗传学研究 小睑裂综合征 FOXL2基因 Sanger测序 多重连接探针扩增技术 

分 类 号：R777.1[医药卫生—眼科]