French Reference Centre for Inherited Epidermolysis Bullosa, Archet Hospital, BP 3079, 06202, NICE Cedex3, France; INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, Faculty of Medicine, 28 Avenue Valombrose, F-06107, Nice, France.
Br J Dermatol. 2014 Apr;170(4):901-6. doi: 10.1111/bjd.12741.
Aplasia cutis congenita (ACC) has been associated with all clinical forms of inherited epidermolysis bullosa (EB), including dominant and recessive dystrophic EB (DDEB and RDEB). To date, only a few patients with DEB specifically combined with ACC have been described and genotyped and almost all cases represent dominant forms of the condition.
The aim of this study was to describe new mutations of COL7A1 in patients with DEB and ACC and investigate possible genotype-phenotype correlations.
Twenty-two patients with DEB and ACC were included among the 123 patients with DEB whose COL7A1 mutations have been identified in the Reference Centre in Nice.
Seven patients presented a severe generalized RDEB phenotype (RDEB-sev-gen), while the other 15 suffered from milder phenotypes. We identified 28 mutations in COL7A1, of which nine are novel. Patients with severe phenotypes have mostly mutations leading to premature termination codon (PTC) and/or splice-site or missense mutations. Patients with the milder phenotypes have mostly glycine or arginine substitutions associated or not with other types of mutations. All amino acid substitutions fell within the carboxyl portion of the triple helix domain (THD) of collagen VII, close to the THD interruptions.
Our findings suggest that ACC is a frequent manifestation in patients with DEB irrespective of the severity of the disease, and is due to leg rubbing in utero. In children with a moderate form of DEB with no or moderate skin fragility, a glycine substitution near the THD interruption domain of the collagen VII leading to thermolabile protein could explain this phenomenon.
先天性表皮松解症（ACC）与所有遗传性大疱性表皮松解症（EB）的临床类型有关，包括显性和隐性营养不良性 EB（DDEB 和 RDEB）。迄今为止，仅描述和进行基因分型的少数 DEB 患者与 ACC 合并，且几乎所有病例均代表该疾病的显性形式。
本研究旨在描述 DEB 和 ACC 患者中 COL7A1 的新突变，并探讨可能的基因型-表型相关性。
在尼斯参考中心鉴定的 123 例 DEB 患者中，有 22 例患者患有 DEB 和 ACC。
7 例患者表现为严重的全身性 RDEB 表型（RDEB-sev-gen），而其余 15 例患者的表型较轻微。我们在 COL7A1 中发现了 28 种突变，其中 9 种是新的。严重表型患者大多存在导致提前终止密码子（PTC）和/或剪接位点或错义突变的突变。表型较轻的患者大多存在甘氨酸或精氨酸取代，这些取代与其他类型的突变有关或无关。所有氨基酸取代都发生在 VII 型胶原三螺旋域（THD）的羧基部分，靠近 THD 中断。
我们的研究结果表明，ACC 是 DEB 患者的常见表现，与疾病的严重程度无关，是由于宫内摩擦所致。在具有中度 DEB 且皮肤脆弱性低或中度的儿童中，VII 型胶原 THD 中断区域附近导致热不稳定蛋白的甘氨酸取代可解释这一现象。
