COL7A1基因致病变异所致新生儿期大疱表皮松解症28例病例系列报告

Retrospective analysis of 28 Chinese newborns with epidermolysis bullosa caused by pathogenic variations of COL7A1 gene

目的了解COL7A1基因导致的大疱表皮松解症(EB)的致病变异谱,以及热点致病变异,并初步分析COL7A1基因的不同遗传模式与新生儿期皮损严重程度的相关性。方法纳入复旦大学附属儿科医院新生儿科住院,临床诊断为大疱表皮松解症,且高通量测序检测到COL7A1基因致病变异/可疑致病变异的患儿。对于患儿的临床表现进行归纳总结,并进行表型-基因型相关性分析。结果共纳入患儿28例,常染色体显性遗传(AD) 5例,常染色体隐性遗传(AR) 23例,皮损、皮肤缺失和其他临床发现在AD和AR模式EB差异均无统计学意义。AD模式EB疾病起始期的皮肤病变累及部位与疾病极期相比,差异无统计学意义(χ2=0.668,P=0.414);AR模式EB疾病起始期的皮肤病变累及部位与疾病极期相比,差异有统计学意义(χ2=16.896,P<0.01);疾病起始期和疾病极期AD模式EB与AR模式EB的皮肤病变累及百分比相比,差异均无统计学意义(P分别为0.131和0.071)。共检测到COL7A1基因的54个变异位点,包括30个(55.6%)已知致病变异,21个新发致病变异,3个临床意义不明,其中最常见的致病变异位点分别是c.8569G>T(p.E2857X) 4例、c.36253636delinsC(p.S1209Lfs*6) 3例、c. 40894090delinsC (p. P1364Lfs*35) 3例。结论不同遗传模式(AR或AD)下COL7A1基因致病变异导致的新生儿期EB,皮损、皮肤缺失和其他临床发现差异无统计学意义,AR模式EB疾病极期较起病初期皮肤病变更广泛。

Objective To understand the pathogenic variation spectrum and the hotspot variation of COL7A1 gene in epidermolysis bullosa(EB),and to analyze the correlation between different inheritance patterns of COL7A1 gene and the severity of skin lesions in neonatal period.Methods We collected neonates diagnosed as EB caused by COL7A1 gene pathogenic or likely pathogenic variants detected by high⁃throughput sequencing from Department of Neonatology of Children's Hospital of Fudan University.The clinical manifestations of them were summarized,and the phenotype⁃genotype correlation was analyzed.Results A total of 28 EB newborns were enrolled including 5 cases of autosomal dominant(AD)inheritance and 23 cases of autosomal recessive(AR)inheritance.There was no significant difference between AD and AR mode EB in skin lesions,skin loss and other clinical findings.There was no statistically significant difference between the initial stage and the extreme stage of skin lesions in AD mode EB(χ2=0.668,P=0.414).The skin lesions in AR mode EB at the initial stage were significantly different from those at the extreme stage(χ2=16.896,P<0.01).There was no significant difference in the percentage of skin lesions in AD mode EB and AR mode EB in the initial and extreme stages of disease(P=0.131,P=0.071).Fifty⁃four COL7A1 pathogenic variants were detected,including 30(55.6%)known pathogenic variants,21 novel pathogenic variants and 3 with unclear clinical significance.The hotspot pathogenic variants were c.8569G>T(p.E2857X)in 4 cases,c.3625_3636delinsC(p.S1209Lfs∗6)in 3 cases and c.4089_4090delinsC(p.P1364Lfs∗35)in 3 cases.Conclusion It has no characteristic changes in skin lesions,skin loss and other clinical findings between different inheritance(AR or AD)in EB caused by pathogenic variation of COL7A1 gene in neonatal period.The scope of skin findings of AR mode in the extreme stage is more extensive than that in the initial stage.