摘要
目的分析两个营养不良型大疱性表皮松解症家系的临床特点和致病基因,揭示疾病的发生机制和患者表型差异机制。方法从两家系成员的外周血中提取DNA进行高通量测序及Sanger测序验证。结果临床资料分析显示,2个家系先证者的临床表现符合营养不良型大疱性表皮松解症的诊断,其中家系1先证者症状明显重于家系中其他患者。基因测序结果显示,家系1患者均携带COL7A1基因c.6082G>C(p.G2028R)突变,同时先证者及其表型正常的母亲和舅舅还携带该基因致病性剪切位点突变c.7068+2(IVS91)T>G,为首次报道致病突变。家系2先证者携带COL7A1基因c.6081_6082 ins C(p.G2028Rfs*71)突变和首次报道的c.1892 G>A(p.W631X)突变,分别来自其父母。结论家系1先证者同时携带2个致病突变可能是其严重临床表型的分子机制;首次报道的COL7A1基因突变丰富了该基因突变谱。
Objective To analyze clinical characteristics of and causative genes in two families with dystrophic epidermolysis bullosa,and to reveal the pathogenesis of the disease and mechanisms underlying phenotypic differences between patients.Methods DNA was extracted from peripheral blood samples of two family members,and subjected to high-throughput sequencing and Sanger sequencing.Results The clinical manifestations of the 2 probands in the 2 families were consistent with the diagnosis of dystrophic epidermolysis bullosa,and the symptoms of the proband in family 1 were more serious than those of other patients in the family.Genetic testing showed that all patients in family 1 carried a mutation c.6082G>C(p.G2028R)in the COL7A1 gene,and the proband and her phenotypically normal mother and uncle also carried a splice-site mutation c.7068+2(IVS91)T>G in the COL7A1 gene,both of which were first reported.The proband in family 2 carried a mutation c.6081_6082 ins C(p.G2028Rfs*71)and the first reported mutation c.1892G>A(p.W631X)in the COL7A1 gene,which were inherited from her father and mother,respectively.Conclusion The two pathogenic mutations may be the molecular mechanism underlying the severe clinical phenotype in the proband in family 1;the first reported mutations enriched the mutation spectrum of the COL7A1 gene.
作者
王莉
任增果
娄桂予
张玉薇
杨科
雷星星
张冰
廖世秀
郝冰涛
Wang Li;Ren Zengguo;Lou Guiyu;Zhang Yuwei;Yang Ke;Lei Xingxing;Zhang Bing;Liao Shixiu;Hao Bingtao(Henan Institute of Medical Genetics,Henan Provincial People′s Hospital,Zhengzhou University People′s Hospital,Henan University People′s Hospital,Zhengzhou 450003,Henan;Henan Institute of Medical Genetics,Henan University People′s Hospital,Henan Provincial People′s Hospital,Zhengzhou 450003,Henan)
出处
《中华皮肤科杂志》
CAS
CSCD
北大核心
2023年第8期770-773,共4页
Chinese Journal of Dermatology
基金
河南省医学科技攻关计划项目(2018020388)。