小睑裂综合征家系FOXL2基因突变检测分析

Mutation analysis of FOXL2 gene in a Chinese family with Blepharophi-mosis-ptosis-epicanthus inversus syndrome

目的探讨小睑裂综合征(BPES)遗传学发病机制,确定BPES家系临床表型,检测FOXL2基因突变位点。方法收集并追溯调查BPES大家系全体家系成员,对其进行全面体格检查及眼部专科检查;对已收集到的BPES家系中全部患者按照眼科分型标准进行确诊、分型,即遗传学的表型确定;所有现存家系成员性激素水平及卵巢功能检测(女性),女性患者行腹部B超检查,BEPS伴卵巢早衰(POF)患者行人体绒膜促性腺激素(HCG)兴奋试验。全体家系成员取外周血5 m L,常规提取DNA,纯化后的PCR产物送测序。结果该家系共24人,现存17人,其中BPES患者7例,现存6例BPES患者中,女性患者均存在生殖异常,为BEPSⅠ型,进一步完善该家系全部成员的体格检查及女性患者卵巢功能检查、人绒毛膜促性腺激素兴奋试验、血清学检查结果,支持POF的临床诊断。基因测序检测到FOXL2基因:C.429C>A(提前的中止密码)。结论系谱分析表明该家系遗传方式为常染色体显性遗传,常染色体显性BPES存在遗传异质性,同一家系中不同个体间也有不同;基因测序检测到的FOXL2基因:C.429C>A(提前的中止密码)突变为新的突变位点。

Objective To investigate the pathogenesis of blepharophimosis-ptosis-epicanthus inversus syndrome（BPES）,and confirm the clinical phenotype of this family with BPES Ⅰ and find the mutation of FOXL2 gene. Methods BPES family were collected and researched directly, and the pedigree was sketched. Strict ophthalmic examination was given to all the family members. All the examination results were collected and analyzed digitally. They were detected with sex hormone level and ovary function（female）. The female patients were detected with B ultrasonic examination on abdomen. The female BPES patients with POF were detected by HCG stimulation test. 5 m L peripheral blood was collected from the proband and the members of the family. Genomic DNA of the peripheral blood from each of the family members was extracted with routine phenol-chloroform method. After purification of PCR production, all the DNA sequences were automatically determined with double deoxidation termination method commercially. The mutation detection was applied to the family members. Results Retrospective survey was made for 24 members from this BPES family,among whom 7 cases were BPES patients and direct survey was made for 17 living members, among whom 6 cases were alive, all female suffered from reproductive abnormalities, were the BEPS type I. Further improved the physical examination of all the family members, ovarian function, HCG excited tests of women, serological test results, all these results supported the clinical diagnosis of POF. FOXL2：C.429C〉A（an untimely terminal code） was detected by gene sequencing. Conclusion The inheritance mode of BPES is autosomal dominant inheritance; the clinical presentation（phenotype） of BPES varied in different individual cases; new gene mutations are found in this family： C.429C〉A, an untimely terminal code.