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首页> 外文期刊>Archives of dermatological research. >Structural changes in epidermal scale and appendages as indicators of defective TGM1 activity.
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Structural changes in epidermal scale and appendages as indicators of defective TGM1 activity.

机译：表皮鳞片和附肢的结构变化是缺陷TGM1活性的指标。

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Defective transglutaminase 1 (TGM1) is a causative factor in some cases of lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE) despite large differences in the phenotype between these conditions. In some of these individuals, defective cornified envelopes (CEs) have been reported by light or electron microscopic examination in epidermal scale, nail and/or hair. These findings suggest that assessment of such defects could have a diagnostic utility in distinguishing TG1-deficient versus non-deficient cases of autosomal recessive ichthyosis (ARI) . Present work (a) examines the integrity of CEs in epidermal scale and appendages in a case of TGM1-deficient CIE, (b) assesses the utility of hairail versus scale analysis in the diagnosis of TGM1 deficiency in vivo and (c) helps characterize the consequences of the V518M mutation in TGM1, about which conflicting reports have appeared. To this end, epidermal scale or callus, nail and hair samples from a patient with TGM1-deficient CIE, his asymptomatic family members and control subjects were extracted vigorously in sodium dodecyl sulfate and dithiothreitol and examined by light (phase contrast) and electron microscopy. Both epidermal scale and nail from the index case lacked the prominent cell borders that were visible by phase contrast microscopy after detergent extraction of control samples. (By contrast, abundant envelope structures were visible in extracted epidermal scale from patients with ichthyosis vulgaris, loricrin keratoderma and epidermolytic hyperkeratosis.) Electron microscopy confirmed the paucity of intact CEs, and revealed further that hair cuticle cells from the same subject also lacked the marginal bands that are visible in control hair samples. Such aberrations were evident neither in the samples from asymptomatic relatives of the index case nor in the hair-cuticle cells of numerous normal individuals, evidence that this defect is not a common polymorphism. These studies extend our prior work on TGM1-deficient LI to thefull spectrum of TGM1-deficient patients, showing that the CIE phenotype, when attributable to a V518M heterozygous mutation in TGM1 in combination with an inactive allele, confers a cross-linking deficiency in a variety of keratinizing epithelia, as previously shown for TGM1-negative LI. These results further suggest that a non-invasive assessment of scale, nail and hair could be of diagnostic utility in distinguishing patients across a full range of phenotypes with deficiency in TGM1-encoded transglutaminase activity from other causes of ARI.
机译：尽管这些条件之间的表型差异很大，但在某些情况下，板层鱼鳞病（LI）和先天性鱼鳞状红皮病（CIE）的转谷氨酰胺酶1（TGM1）仍是致病因素。在这些个体中的一些中，通过光或电子显微镜检查已经在表皮规模，指甲和/或头发上报告了不良的角质化包膜（CE）。这些发现表明，对此类缺陷的评估可在区分常染色体隐性鱼鳞状鱼病（ARI）的TG1缺陷和非缺陷病例中具有诊断作用。当前的工作（a）在TGM1缺乏CIE的情况下检查了表皮鳞片和附肢的CE完整性，（b）评估了头发/指甲与鳞片分析在体内诊断TGM1缺失的实用性，并且（c）帮助表征TGM1中V518M突变的后果，有关该问题的报道已经出现。为此，从十二烷基硫酸钠和二硫苏糖醇中大力提取TGM1缺陷型CIE患者，无症状家庭成员和对照对象的表皮鳞屑或愈伤组织，指甲和头发样品，并进行光（相差）和电子显微镜检查。表皮的鳞片和索引病例的指甲都没有突出的细胞边界，在对照样品去污剂提取后，相差显微镜可以看到这些边界。 （相比之下，寻常性鱼鳞病，Loricrin角化皮病和表皮溶解性角化过度的患者，在提取的表皮鳞片上可见大量的包膜结构。）电子显微镜证实了完整CE的缺乏，并且进一步揭示了同一受试者的毛鳞片细胞也缺乏边缘对照发样品中可见的条带。在来自无症状亲属的样本中以及在许多正常个体的毛鳞片细胞中均未发现这种畸变，这证明该缺陷不是常见的多态性。这些研究将我们先前对TGM1缺陷型LI的研究扩展到TGM1缺陷型患者的全谱，表明CIE表型当归因于TGM1中的V518M杂合突变与无活性等位基因结合时，赋予了CGM表型交联缺陷。如先前针对TGM1阴性的LI所显示的，各种角化上皮细胞。这些结果进一步表明，鳞屑，指甲和头发的非侵入性评估可能具有诊断意义，可用于将跨越TGM1编码的转谷氨酰胺酶活性不足的各种表型与其他原因的ARI病人区分开。

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