CAJ | 학술논문

目的报道1例来自山东的类脂蛋白沉积症家系,研究其家系成员的细胞外基质蛋白(ECM1)基因突变.方法类脂蛋白沉积症家系3代8名成员,有2例患者,分别为先证者(Ⅲ1)及其母亲(Ⅱ2),均表现为睑缘丘疹、舌系带增厚变短及声音嘶哑.间接喉镜检查显示声带浸润增厚.睑缘及喉部黏膜组织病理检查均提示真皮透明蛋白样物质沉积,PAS染色强阳性,淀粉酶染色阴性,病理诊断符合类脂蛋白沉积症.采用DNA直接测序检测家系8例成员ECM1基因,巢式PCR琼脂糖凝胶电泳对患者的ECM1编码区进行基因突变分析.取100例正常汉族人基因组DNA样品做对照.结果 2例患者均为遗传复合体,先证者母亲(Ⅱ2)ECM1的两个等位基因分别存在3个错义突变(p.P169T,p.A44T,p.R392W).先证者除了从其母亲遗传来的一个错义突变外(p.P169T),还有从其父亲(Ⅱ1)遗传来的一个同义突变(c.879G＞ A),这个突变产生一个潜在的剪切受体位点“AG”,巢式PCR琼脂糖凝胶电泳结果和PCR产物测序结果证实,该同义突变导致ECM1基因的剪切发生改变.结论本类脂蛋白沉积症家系存在新的ECM1基因同义突变导致的剪切突变.
목적 보도1례래자산동적류지단백침적증가계,연구기가계성원적세포외기질단백(ECM1)기인돌변.방법 류지단백침적증가계3대8명성원,유2례환자,분별위선증자(Ⅲ1)급기모친(Ⅱ2),균표현위검연구진、설계대증후변단급성음시아.간접후경검사현시성대침윤증후.검연급후부점막조직병리검사균제시진피투명단백양물질침적,PAS염색강양성,정분매염색음성,병리진단부합류지단백침적증.채용DNA직접측서검측가계8례성원ECM1기인,소식PCR경지당응효전영대환자적ECM1편마구진행기인돌변분석.취100례정상한족인기인조DNA양품주대조.결과 2례환자균위유전복합체,선증자모친(Ⅱ2)ECM1적량개등위기인분별존재3개착의돌변(p.P169T,p.A44T,p.R392W).선증자제료종기모친유전래적일개착의돌변외(p.P169T),환유종기부친(Ⅱ1)유전래적일개동의돌변(c.879G＞ A),저개돌변산생일개잠재적전절수체위점“AG”,소식PCR경지당응효전영결과화PCR산물측서결과증실,해동의돌변도치ECM1기인적전절발생개변.결론 본류지단백침적증가계존재신적ECM1기인동의돌변도치적전절돌변.
Objective To report a family with lipoid proteinosis (LP) from Shandong province and to analyze mutations in the extracellular matrix protein 1 (ECM1) gene in this family.Methods Eight members in a threegeneration family with LP were clinically investigated,and two patients were identified to suffer from LP,including the proband (Ⅲ 1) and her mother (Ⅱ 2).Both of the patients presented with papules on the palpebral margin,short and thick lingual frenum,and hoarseness.Indirect laryngoscopy showed infiltrating and thickening of the vocal cord.Pathological examination of lesions on the palpebral margin and laryngeal mucosa revealed deposits of hyaline-like material in the dermis,which was strongly positive for periodic acid-Schiff (PAS) staining and resistant to diastase digestion.The pathological diagnosis was LP.Blood samples were collected from all the family members and 100 ethnically matched,unrelated and unaffected Chinese human controls followed by DNA extraction.PCR and sequencing were performed to detect the ECM1 gene,and nested PCR followed by agarose gel electrophoresis to analyze mutations in the coding region of the ECM1 gene.Results Both of the two patients were compound heterozygotes.Three missense mutations,incluing p.P169T,p.A44T and p.R392W,were found in the ECM1 gene of the affected mother,with p.P169T in one allele and p.A44T as well as p.R392W in the other.The girl patient inheried the missence mutation p.P169T from her mother and a synonymous mutation c.879G ＞ A from her father (Ⅱ 1).Nested PCR showed that the c.978G ＞ A mutation generated a splice-acceptor site "AG",which leaded to a splicing defect.Conclusion A novel synonymous splice-acceptor site mutation c.879G ＞ A in the ECM1 gene is identified in the family with LP.