一例显性营养不良型大疱性表皮松解症的基因突变检测

目的 研究1例营养不良型大疱性表皮松解症家系中的基因突变情况.方法 经组织病理、电镜及免疫荧光方法结合临床诊断为显性营养不良型大疱性表皮松解症1例,采用聚合酶链反应(PCR)DNA直接测序,限制性内切酶反应及应用D3S1359、D20S161、D5S818、D17S1293、CSFIPO五个座位微卫星DNA多态标志的方法对此例患者家系进行基因突变情况检测.结果 家系中患者存在COL7A1上第6240位鸟嘌呤G被腺嘌呤A替代突变导致Ⅶ胶原第2043位的甘氨酸被精氨酸替代,而其父母及对照的健康人均不存在此突变.结论 G2043R是引起该家系临床病变的特异突变,不是多态性变化,且此突变为一个denovo突变.     

痒疹样营养不良型大疱性表皮松解症一家系的基因突变

目的 鉴定一痒疹样营养不良型大疱性表皮松解症家系的基因突变,为进一步开展基因诊断和基因治疗奠定基础.方法 应用聚合酶链反应(PCR)、DNA直接测序明确突变位点,根据突变位点设计等位基因特异性引物,用PCR来检测突变位点以及采用逆转录-聚合酶链反应(RT-PCR)和克隆测序进一步确定该家系的致病原因.结果 该家系中患者COL7A1基因的87号外显子存在剪接位点突变,导致87号外显子被剪切,Ⅶ型胶原的胶原区合成后缺少了23个氨基酸.健康对照不存在此突变.结论 COL7A1基因剪接位点的突变是引起该家系临床症状的特异突变,而非多态性改变.     

Clinical Criteria for Differentiating between Recessive and Dominant Forms of Dystrophic Epidermolysis Bullosa,Elaborated from an Analysis of 119 Cases

We attempted to establish clinical criteria which differentiated between recessive dystrophic epidermolysis bullosa (RDEB) and dominant DEB (DDEB), since these two groups show prominent differences in prognosis, genetic recurrence risk and response to some types of treatment. The total of 119 cases examined consisted of our own 9 cases (2 of RDEB and 7 of DDEB) and 110 cases (26 of RDEB and 84 of DDEB) collected from the medical literature. They were analyzed by calculating the sensitivity and specificity of ten clinical features. We concluded that, syndactyly, presence of complications, dental lesions, remission-less course, and oral lesions are strongly indicative of RDEB (more than 70% specific). Intractable skin ulcer is suggestive of RDEB (more than 55% specific). Nail lesions, scar and atrophy, milia and pigmentation are not helpful in the differentiation because of their commonality. The proposed criteria are simple, reliable, and practical, providing us with a useful tool for differentiation of RDEB and DDEB in daily practice.     

Compound Heterozygosity of Dominant and Recessive COL7A Alleles in a Severely Affected Patient with a Family History of Dystrophic Epidermolysis Bullosa: Clinical Findings,Genetic Testing,and Treatment Implications

An 8‐year‐old girl born to a family with more than three generations of dominant dystrophic epidermolysis bullosa (DDEB) presented with life‐threatening confluent skin erosions, mitten hand deformity, and failure to thrive. Reassessment of her family history and genetic testing showed compound heterozygous COL7A mutations, one inherited from her DDEB‐affected mother and one from her unaffected, healthy father. This family illustrates the risk of unexpected, severe, autosomal recessive epidermolysis bullosa (EB) in a family with milder, multigenerational autosomal dominant EB. Clinicians should recognize the clinical spectrum of dystrophic EB and recommend genetic consultation when the phenotype conflicts with family history.     

“Nails Only” Phenotype and Partial Dominance of p.Glu170Lys Mutation in a Family with Epidermolysis Bullosa Simplex

Epidermolysis bullosa (EB) is a heterogeneous group of rare, chronic, inherited skin disorders characterized by marked mechanical fragility of epithelial tissues, with blistering and erosions after minor trauma. We present the first report of a nails‐only phenotype in two patients with epidermolysis bullosa simplex (EBS) and a heterozygous pGlu170Lys mutation and the second reported case of EBS associated with a homozygous p.Glu170Lys mutation in the KRT5 gene. Our findings may be relevant for genetic counseling and for understanding the inheritance pattern of EBS.