背景:在过去的10年里,在罗马尼亚,大疱性表皮松解症(EB)患者的福利方面取得了进展.在五所大学医院,隶属于国家罕见疾病治疗计划,训练有素的专家诊断和治疗这种罕见疾病的患者。关于诊断,由于无法获得免疫荧光作图和分子遗传分析,因此仍然存在局限性,一般不报销。我们的目标是介绍在Colentina临床医院诊断EB患者的经验,强调在我们的患者队列中观察到的基因型-表型相关性。
方法:对2012年至2024年间入选的患者的记录进行分析,考虑到临床方面,and,当可用时,免疫荧光作图,透射电子显微镜,和遗传分子分析。
结果:确定了56名患者,其中31例营养不良性EB,三个是交界性EB,11个为单纯形EB。对于11个案例,无法确定EB类型。关于EB单工,2例KRT5突变患者和3例KRT14突变患者具有不同的临床表达,从轻度表型到重度表型,已确定。我们的数据库中登记了三名严重交界性EB患者,其中一名患者,在LAMA3基因中发现了两个以前未报告的突变.关于营养不良性EB,确定了31例,其中隐性营养不良25例,显性营养不良6例。对15名患者进行了分子遗传学检测,最常见的变异是c.425A>G,在六个案例中被确认。
结论:确定了两个以前未报告的突变,即,COL7A1c.5416G>C,轻度表型患者的杂合错义变异,主要是指甲受累,和COL7A1c.5960del,一种在外显子72中产生移码的变体,导致过早的终止密码子;该变体在两个患有严重隐性营养不良的兄弟姐妹中被鉴定。
结论:在确定正确和完整的诊断方面已经采取了重要步骤,以及我们参考中心的EB患者特征。这些发现强调了分子遗传检测在确认诊断和阐明遗传模式方面的关键作用。特别是在非典型表现或从头突变的情况下。
BACKGROUND: During the last 10 years, in Romania, progress has been made for the welfare of patients suffering from epidermolysis bullosa (EB). In five university hospitals, affiliated with the National Program for the Treatment of Rare Diseases, highly trained specialists diagnose and treat patients with this rare condition. Regarding diagnosis, limitations still exist as immunofluorescence mapping and molecular genetic analysis are not accessible, and generally not reimbursed. Our objective is to present the experience in diagnosing EB patients at Colentina Clinical Hospital, highlighting genotype-phenotype correlations observed in our cohort of patients.
METHODS: The records of the patients enrolled between 2012 and 2024 were analyzed considering clinical aspects, and, when available, immunofluorescence mapping, transmission electron microscopy, and genetic molecular analysis.
RESULTS: Fifty-six patients were identified, of whom 31 cases were of dystrophic EB, three were of junctional EB, and 11 were of simplex EB. For 11 cases, the EB type could not be determined. Regarding EB simplex, two patients with KRT5 mutations and three patients with KRT14 mutations with various clinical expressions, from mild phenotype to severe forms, were identified. Three severe junctional EB patients were registered in our database and for one of the patients, two previously unreported mutations in the LAMA3 gene were identified. Regarding dystrophic EB, 31 cases were identified, of which 25 were recessive dystrophic cases and six were dominant dystrophic cases. Molecular genetic testing was performed for 15 patients, and the most common variant was c.425A>G, identified in six cases.
CONCLUSIONS: Two previously unreported mutations were identified, namely, COL7A1 c.5416G>C, a heterozygous missense variant in a patient with a mild phenotype, mainly with nail involvement, and COL7A1 c.5960del, a variant that generates a frameshift in exon 72 resulting in a premature stop codon; this variant was identified in two siblings with a severe recessive dystrophic.
CONCLUSIONS: Important steps have been made in identifying the correct and complete diagnosis, as well as the characterization of EB patients addressing our reference center. The findings underscore the pivotal role of molecular genetic testing in confirming diagnoses and elucidating inheritance patterns, especially in cases with atypical presentations or de novo mutations.