两个中国籍先天性眼外肌纤维化家系基因定位与临床分型

Genetic localization and clinical classification of congenital fibrosis of the extraocular muscles in 2 Chinese families

目的通过候选基因法对2个中国籍先天性眼外肌纤维化(congenital fibrosis of the extraocular muscles,CFEOM)家系进行致病基因定位及疾病分型。方法对2个CFEOM家系所有成员均采集病史、体格检查、抽取外周静脉血5~8 mL并提取基因组DNA。选择KIF21A第2、8、20、21外显子;PHOX2A/ARIX第1、2、3外显子;TUBB2B第1、2、3、4外显子;TUBB3第1、2、3、4外显子区域进行PCR引物合成并将扩增样品进行纯化测序,结果应用Chromas 2.3及DNAman 7.0软件进行序列比对分析。结果家系1五代中9人患病,均具有典型CFEOM外观特征。致病基因位于KIF21A基因外显子21,2860C>T。家系2四代中4人患病,除1人临床表型不典型外,其他3人都具有典型的CFEOM外观特征。致病基因位于TUBB3基因外显子4,1249G>A。结论运用候选基因法可快捷、有效地确定遗传性疾病家系的致病基因。家系1属于CFEOM 1A型,为常染色体完全外显的显性遗传;家系2属于CFEOM 3A型,为常染色体不完全外显的显性遗传。

ObjectiveTo determine the pathogenic mutant gene and the classification for2Chinese families with congenital fibrosis of the extraocular muscles(CFEOM)by using candidate genes methods.MethodsAll members in the2Chinese families with CFEOM were collected and underwent for clinical data collection,including medical history,physical examination and5-8mL peripheral venous blood for DNA extraction.Exon2,8,20,21of KIF21A,exon1,2,3of PHOX2A/ARIX,exon1,2,3,and4of TUBB2B and exon1,2,3,4of TUBB3were selected and synthesized by PCR,and the amplified samples were purified for sequences analysis by Chromas2.3and DNAman7.0software.ResultsThere were9members developed CFEOM in family1,with the typical CFEOM characteristics.The mutation site was located in KIF21A(exon21),2860C>T;and4patients in family2suffered this disease,and the typical CFEOM appearance features was in3patients.The mutation site was located in TBUU3(exon4),1249G>A.ConclusionThe candidate genes methods can be used to identify the pathogenic genes of pedigrees with inherited diseases effectively.Family1belongs to CFEOM1A type,which is the autosomal dominant inheritance with complete penetrance,and family2belongs to CFEOM3A type,whivh is the autosomal dominant inheritance with incomplete penetrance.