CAJ | 학술논문

目的分析3个Fabry病家系GLA基因突变及其与临床表型的关系.方法应用PCR结合DNA测序技术,检测先证者及相关成员GLA基因编码序列与剪切位点DNA序列变异,分析致病性突变与临床表型关系.结果在家系1先证者GLA基因第5外显子中发现1个未经报道的错义突变c.797A＞C(D266A),家系2先证者GLA基因第5外显子中发现1个错义突变c.644A＞G(N215S),家系3先证者GLA基因第2外显子中发现1个无义突变c.355C＞T(Ql19X).家系1与家系3先证者主要表现为皮肤损害和慢性肾功能不全,家系2先证者临床则以肥厚性心肌病为特点.结论首次发现的GLA基因c.797A＞C(D266A)突变是第266位密码子第6个被证实的错义突变,已报道的另5种突变均有致病性,在正常非相关对照中未发现该突变,提示GLA基因c.797A＞C突变很可能是该家系的致病原因.N215S和Q119X系首次发现于中国Fabry病家系的突变.GLA基因不同位点的突变具有较为显著的表型差异.
목적 분석3개Fabry병가계GLA기인돌변급기여림상표형적관계.방법 응용PCR결합DNA측서기술,검측선증자급상관성원GLA기인편마서렬여전절위점DNA서렬변이,분석치병성돌변여림상표형관계.결과 재가계1선증자GLA기인제5외현자중발현1개미경보도적착의돌변c.797A＞C(D266A),가계2선증자GLA기인제5외현자중발현1개착의돌변c.644A＞G(N215S),가계3선증자GLA기인제2외현자중발현1개무의돌변c.355C＞T(Ql19X).가계1여가계3선증자주요표현위피부손해화만성신공능불전,가계2선증자림상칙이비후성심기병위특점.결론 수차발현적GLA기인c.797A＞C(D266A)돌변시제266위밀마자제6개피증실적착의돌변,이보도적령5충돌변균유치병성,재정상비상관대조중미발현해돌변,제시GLA기인c.797A＞C돌변흔가능시해가계적치병원인.N215S화Q119X계수차발현우중국Fabry병가계적돌변.GLA기인불동위점적돌변구유교위현저적표형차이.
Objective Fabry disease is a rare lysosome storage disease featuring X-linked recessive inheritance.The study was to explore potential mutations of alpha-galactosidase A (GLA) gene and their correlation with clinic manifestations in three Chinese pedigrees with Fabry disease.Methods All exons and flanking sequences of GLA gene were amplified with PCR.Potential mutations were detected with bidirectional DNA sequencing.Correlation between particular mutations and clinic features were analyzed.Results A unreported missense mutation,c.797A＞C (D266A) in GLA exon 5 was identified in pedigree 1.Also in exon 5,a missense mutation c.644A＞G (N215S) was found in pedigree 2.In pedigree 3,a nonsense mutation c.355C＞T (Q119X) was found in exon 2.The c.797A＞C mutation was not detected in 200 unrelated male controls.The probands of pedigrees 1 and 3 had presented mainly with skin damage and chronic renal insufficiency,whilst the proband of pedigree 2 had presented with hypertrophic cardiomyopathy.Conclusion The unreported c.797A＞C (D266A) mutation is the sixth missense type mutation of the 266th codon of GLA gene,and all other 5 missense mutations reported previously had been confirmed to be responsible for Fabry disease.The c.797A＞C mutation,not found in 200 unrelated male controls,may be the causative mutation in pedigree 1.The c.644A＞G and c.355C＞T mutations were first detected in Chinese patients.Variable phenotypes of Fabry disease may be in part attributed to the natures of particular mutations of GLA gene.