CAJ | 학술논문

目的对常染色体显性遗传晶状体脱位( EL)一家系进行致病基因研究.方法通过询问病史及系谱分析确定遗传模式.对所有患者进行临床检杳,包括眼部、心脏以及骨骼确定临床表型.采集患者外周静脉血5 ml,提取基因组DNA.采用微卫星标记引物,通过连锁分析进行致病基因定位,两点法计算LOD值.采用直接测序法对致病基因全部外显子,以及外显子与内含子拼接部进行基因序列分析.结果该家系为常染色体显性遗传模式.经连锁分析,将致病基因定位于常染色体15q21.1区间,并在微卫星位点D15S978获得最大LOD值为3.01.基因序列分析发现候选基因FBN1 29外显子发生c.C3519G.(p.N1173K)杂合性基因突变,而家系正常人以及100名正常对照无此基因突变.结论 FBN1基因N1173K突变是导致该家系临床表型的主要原因.
목적 대상염색체현성유전정상체탈위( EL)일가계진행치병기인연구.방법 통과순문병사급계보분석학정유전모식.대소유환자진행림상검묘,포괄안부、심장이급골격학정림상표형.채집환자외주정맥혈5 ml,제취기인조DNA.채용미위성표기인물,통과련쇄분석진행치병기인정위,량점법계산LOD치.채용직접측서법대치병기인전부외현자,이급외현자여내함자병접부진행기인서렬분석.결과 해가계위상염색체현성유전모식.경련쇄분석,장치병기인정위우상염색체15q21.1구간,병재미위성위점D15S978획득최대LOD치위3.01.기인서렬분석발현후선기인FBN1 29외현자발생c.C3519G.(p.N1173K)잡합성기인돌변,이가계정상인이급100명정상대조무차기인돌변.결론 FBN1기인N1173K돌변시도치해가계림상표형적주요원인.
Objective To study the disease-causing gene mutation in a Chinese family with ectopia lentis.Methods The phenotype of each family member in a Chinese family with ectopia lentis was identified by detailed clinical examination. The inheritance mode in this family was ascertained by the pedigree analysis.Linkage analysis was performed by microsatellite markers on chromosome 15 and LOD Score was calculated by Mlink program. Gene mutations were detected by sequence analysis to the whole coding region and exon-intron boundaries of the candidate gene. Results A significant LOD score of 3.01 was obtained at D15S978 on chromosome 15q21.1,where FBNI gene was located. A C3519G change in exon 29 of FBNI gene,resulting in asparagine change to lysine at codon 1173,was detected by direct sequence analysis. This mutation was absent in the normal family members and 100 normal controls.Conclusions Our results indicate that c.C3519G (p.N1173K) mutation in FBN1 gene is the underlying molecular pathogenesis of this family with ectopia lentis.(Chin J Ophthalmol,2012,48: