HETEROGENEITY IN HARLEQUIN ICHTHYOSIS, AN INBORN ERROR OF EPIDERMAL KERATINIZATION - VARIABLE MORPHOLOGY AND STRUCTURAL PROTEIN EXPRESSION AND A DEFECT IN LAMELLAR GRANULES
HETEROGENEITY IN HARLEQUIN ICHTHYOSIS, AN INBORN ERROR OF EPIDERMAL KERATINIZATION - VARIABLE MORPHOLOGY AND STRUCTURAL PROTEIN EXPRESSION AND A DEFECT IN LAMELLAR GRANULES
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DOI：
10.1111/1523-1747.ep12873301
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发表时间：
1990-01-01
影响因子：
6.5
通讯作者：
SYBERT, VP
中科院分区：
文献类型：
--
作者：
DALE, BA;HOLBROOK, KA;SYBERT, VP
皮肤活检和规模样本，从九个婴儿和一个胎儿与丑角鱼鳞病（HI）的影响，从八个家庭。表皮分化的形态学和生化标准和细胞培养研究进行了检查。两个显着的异常被确定;第一，角蛋白和聚丝蛋白的表达异常和不同的情况下，第二，在所有情况下，板层颗粒不存在或异常，角质层内的细胞间板层不存在。三个HI表型区分的表皮结构蛋白的可变表达。根据角蛋白K6和K16（“过度增殖”角蛋白）的缺失（1型）或存在（2型和3型）以及毛囊间表皮中纤丝聚集蛋白原的存在（仅1型和2型）对病例进行分类。丝聚蛋白原显然没有转化为丝聚蛋白，但它保留在鳞片中。丝聚蛋白原加工的阻断可能是由于失活的磷酸酶。在两个家庭（1型和2型）的simplex表现出相同的类型分类，表明表型的表达是一致的家庭内，但家庭之间的差异。培养的HI角质形成细胞在相差显微镜下是正常的，但在电子显微镜下是异常的，没有层状颗粒和上层的广泛堆叠。我们的结论是，丑角鱼鳞病是一组遗传异质性的疾病与改变板层颗粒，细胞间脂质，和正常表皮角化的结构蛋白标志物的表达和/或加工的变化。此外，板层颗粒和结构蛋白缺陷可能通过涉及磷酸化/去磷酸化的机制间接相关。
Skin biopsies and scale samples from nine infants and one fetus affected with harlequin ichthyosis (HI) were obtained from eight families. Epidermal differentiation was examined by morphologic and biochemical criteria and cell culture studies. Two striking abnormalities were identified; first, keratin and filaggrin expression were abnormal and varied between cases, and, second, in all cases lamellar granules were absent or abnormal, and intercellular lamellae within the stratum corneum were absent. Three HI phenotypes were distinguished by variable expression of epidermal structural proteins. Cases were classified by the absence (type 1) or presence (types 2 and 3) of keratins K6 and K16 ("hyperproliferative" keratins) and by the presence of profilaggrin in the interfollicular epidermis (types 1 and 2 only). Profilaggrin is apparently not converted to filaggrin, but it is retained in the scale. The block in profilaggrin processing may be due to an inactive phoshatase. Siblings in two families (presenting with types 1 and 2) showed the same type classification suggesting that expression of the phenotype is consistent within families but differs between families. Cultured HI keratinocytes were normal by phase microscopy, but abnormal by electron microscopy with no lamellar granules and extensive stacking of the upper layers. We conclude that harlequin ichthyosis is a genetically heterogeneous group of disorders with altered lamellar granules, intercellular lipids, and variation in expression and/or processing of structural protein markers of normal epidermal keratinization. Furthermore, the lamellar granule and structural protein defects may be indirectly related via a mechanism involving phosphorylation/dephosphorylation.