Department of Genetics, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands.
J Med Genet. 2011 Mar;48(3):160-7. doi: 10.1136/jmg.2010.082230. Epub 2010 Nov 26.
The inversa type of recessive dystrophic epidermolysis bullosa (RDEB-I) is a rare variant of dystrophic epidermolysis bullosa, characterised by blistering in the body flexures, trunk, and mucosa. The cause of this specific distribution is unknown. So far, 20 COL7A1 genotypes have been described in RDEB-I and genotype-phenotype correlations have not been studied extensively. The aim of the study was to gain more insight into the pathophysiology of this intriguing RDEB-I phenotype.
Twenty Dutch and British RDEB-I patients, and full genotypes in 18 of them, were identified. The literature on RDEB-I genotypes was reviewed and an extensive genotype-phenotype correlation study for RDEB-I was conducted.
All 20 patients had generalised blistering at birth and during early infancy. In most patients, the age of transition from generalised to inversa distribution was before the age of 4 years. A spectrum of disease severity, ranging from the mildest 'mucosal only' phenotype to the severest phenotype with limited acral involvement, was noted. The 29 genotypes of these RDEB-I patients and those reported in the literature revealed that RDEB-I is associated with specific recessive arginine and glycine substitutions in the triple helix domain of type VII collagen.
Why these specific arginine and glycine substitutions cause the inversa distribution remains unknown. It was not possible to identify clear differences in location and nature of substituting amino acids between these mutations and missense mutations causing other RDEB phenotypes. It is hypothesised that the higher skin temperature in the affected areas plays an important role in the pathophysiology of RDEB-I.
隐性营养不良型大疱性表皮松解症（RDEB-I）是一种罕见的营养不良型大疱性表皮松解症变体，其特征在于身体弯曲处、躯干和黏膜处出现水疱。这种特定分布的原因尚不清楚。到目前为止，已经在 RDEB-I 中描述了 20 种 COL7A1 基因型，并且尚未广泛研究基因型-表型相关性。本研究旨在更深入地了解这种引人入胜的 RDEB-I 表型的病理生理学。
鉴定了 20 名荷兰和英国的 RDEB-I 患者，其中 18 名患者的完整基因型。回顾了 RDEB-I 基因型的文献，并对 RDEB-I 进行了广泛的基因型-表型相关性研究。
所有 20 名患者在出生和婴儿早期均有全身性水疱。在大多数患者中，从全身性到反转分布的过渡年龄在 4 岁之前。注意到疾病严重程度的范围从最轻微的“仅黏膜”表型到最严重的仅累及远端的表型。这些 RDEB-I 患者和文献中报道的 29 种基因型表明，RDEB-I 与 VII 型胶原三螺旋结构域中特定的隐性精氨酸和甘氨酸取代有关。
为什么这些特定的精氨酸和甘氨酸取代会导致反转分布尚不清楚。无法确定这些突变与引起其他 RDEB 表型的错义突变之间取代氨基酸的位置和性质有明显差异。假设受影响区域的皮肤温度较高在 RDEB-I 的病理生理学中起着重要作用。
