Pretibial dystrophic epidermolysis bullosa: a recessively inherited COL7A1 splice site mutation affecting procollagen VII processing
Pretibial dystrophic epidermolysis bullosa: a recessively inherited COL7A1 splice site mutation affecting procollagen VII processing
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DOI：
10.1046/j.1365-2133.1999.03155.x
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发表时间：
1999-11-01
影响因子：
10.3
通讯作者：
Castiglia, D
中科院分区：
文献类型：
--
作者：
Betts, CM;Posteraro, P;Castiglia, D
胫骨前大疱性表皮松解症 (PEB) 是一种罕见的局部营养不良性大疱性表皮松解症 (EBD)，这是一组异质性遗传性水疱性疾病，其特征是疤痕形成、真皮-表皮粘附力丧失和锚定原纤维 (AF) 改变。 VII 型胶原蛋白基因 (COL7A1) 的突变是 EBD 的基础，并且在显性 FEB 家族中已发现甘氨酸取代突变。我们报告了一名受 FEB 影响的 33 岁男性，显示出异常 AF 和 VII 型胶原蛋白免疫染色减少。 COL7A1 基因突变搜索揭示了 115 外显子-内含子边界 (33563del14) 中的 14 bp 缺失，导致外显子 115 的框内跳跃，并消除了 pro-α 1(VII) 多肽链中的 29 个氨基酸，结果表明，VII 型前胶原未能加工成成熟胶原 Vn 并在真皮-表皮交界处积累。使用NC-2域特异性抗体进行免疫荧光染色，先证者的父亲是临床上未受影响的突变33563del14的杂合子携带者，而母亲的致病性突变尚未确定，这是FEB隐性缺失突变的首次报告，并扩展了与突变33563del14相关的EBD表型范围。
Pretibial epidermolysis bullosa (PEB) is a rare form of localized epidermolysis bullosa dystrophica (EBD), a heterogeneous group of inherited, blistering diseases characterized by scarring, loss of dermal-epidermal adhesion and altered anchoring fibrils (AF). Mutations in the type VII collagen gene (COL7A1) underlie EBD and in a dominant FEB family a glycine substitution mutation has been identified. We report a 33-year-old man affected by FEB showing abnormal AF and reduced immunostaining for type VII collagen. Mutation search in the COL7A1 gene revealed a 14 bp deletion in the 115 exon-intron boundary (33563del14), which resulted in the in-frame skipping of exon 115 with elimination of 29 amino acids from the pro-alpha 1(VII) polypeptide chain, Asa consequence, procollagen VII failed to be processed to mature collagen Vn and accumulated at the dermal-epidermal junction, as revealed by immunofluorescence staining using a NC-2 domain-specific antibody, The proband's father was a clinically unaffected heterozygous carrier of mutation 33563del14, whereas the maternal pathogenetic mutation has still not been identified, This represents the first report of a recessive deletion mutation in FEB and extends the range of EBD phenotypes associated with mutation 33563del14.