先天性眼外肌纤维化伴少年白发家系的KIF21A基因突变分析

目的对先天性眼外肌纤维化(Congenital fibrosis of the extraocular muscles,CFEOM)伴少年白发家系进行候选致病基因KIF21A突变筛查。方法应用Wizard Genomic DNA Purification试剂从家系成员外周静脉血中提取基因组DNA;以先证者基因组DNA为模板,PCR扩增KIF21A基因外显子8、20和21的DNA序列,PCR产物纯化后进行DNA直接测序筛查突变位点。一旦发现可疑性变异,则采用DNA双向测序方法在其他家系成员进行疾病与突变共分离分析以及进一步确认其是否为致病性突变位点。结果该家系三代呈常染色体显性遗传,临床表型大致相同,可确诊为CFEOM1型。KIF21A基因突变筛查发现患者在第21外显子携带c.C2860T杂合性突变,正常成员没有,临床表型与基因型呈共分离。该突变为一个已知突变,可导致KIF21A蛋白第954位的精氨酸变为色氨酸(p.R954W)。结论 KIF21AR954W突变是导致该家系患者眼外肌纤维化致病的遗传基础,是否与少年白发相关尚待进一步研究。

Analysis of KIF21A Mutation in a Congenital Fibrosis of the Extraocular Muscles Kindred Associated with Juvenile Canities

Objective To identify the mutation of the candidate gene KIF21A in a Chinese family with congenital fibrosis of the extraocular muscles(CFEOM) and associated with juvenile canities.Methods Genomic DNA was extracted from peripheral blood leukocytes of the family members by using Wizard Genomic DNA Purification Kit.Three coding exons(8,20 and 21) of the human KIF21A gene were amplified by polymerase chain reaction(PCR).The PCR products were purifiedand sequenced.The sequence variation detected was confirmed in other available family members by bidirectional sequencing.Results The genetic trait of this pedigree was autosomal dominant inheritance and met to CFEOM1 criterion.Direct DNA sequence analysis identified a heterozygous mutation c.C2860T in exon 21 in all affected individuals,but not in unaffected family members,and the clinical phenotypes showed no co-segregation with the disease phenotype.This missense mutation is predicted to result in a tryptophan substitution for arginine in codon 954 of KIF21A.Conclusion KIF21A R954W mutation is the genetic basis of this family with CFEOM1.However,the effect of KIF21A mutation on juvenile canities is still unclear.