Prenatal diagnosis of bullous ichthyosiform erythroderma: detection of tonofilament clumps in fetal epidermal and amniotic fluid cells.

Journal of Medical Genetics (Impact Factor: 5.64). 03/1986; 23(1):46-51. DOI: 10.1136/jmg.23.1.46
Source: PubMed

ABSTRACT The prenatal diagnosis of bullous ichthyosiform erythroderma (BIE) has been achieved at 20 weeks' gestation by electron microscopic identification of a pathognomonic cytoskeletal abnormality within fetal epidermal cells obtained by fetoscopic skin biopsy. The same abnormality was also observed in skin derived amniotic fluid cells. The question whether amniocentesis might be used instead of fetoscopy for future prenatal detection of BIE is discussed.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bullous congenital ichthyosiform erythroderma is a human hereditary skin disorder in which suprabasal keratinocytes rupture. Recent reports have implicated keratins K1 and K10 in this disease. Here we describe four diverse keratin mutations that are all significantly associated with this disease. Two of these are in the helix 1A subdomain of the type II keratin 1, giving a serine-to-proline substitution in codon 185 and an asparagine-to-serine substitution in codon 187. In the analogous region of type I keratin 10, an arginine-to-proline and an arginine-to-serine transition in codon 156 have been identified. All four mutations create restriction fragment length polymorphisms that were used exclude the mutations from 120 normal chromosomes. Insertional polymorphism (in the V2 subdomains of the non-helical tails of K1 and K10) was excluded as the cause of the phenotypic heterogeneity observed within one family.Keywords: EHK (epidermolytic hyperkeratosis), intermediate filaments
    Journal of Investigative Dermatology 12/1993; 102(1):24-30. DOI:10.1111/1523-1747.ep12371726 · 6.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the role of filaggrin in keratin filament aggregation in epidermolytic ichthyosis (epidermolytic hyperkeratosis, EH), we studied EH skin by light and electron microscopic immuno-histochemistry, and biochemical analysis using sodium dodecylsulphate-polyacrylamide gel electrophoresis and immunoblotting. Immunohistochemical staining showed an increased number of filaggrin-immunoreactive cell layers, but the reaction was still confined to the mid- and upper epidermal layers, whereas an abnormal granular pattern of staining for K10 began in the lower suprabasal cell layers. This suggests that the aggregation of kertain filaments precedes, and occurs independently of, profilaggrin synthesis during epidermal differentiation. Although keratohyalin granules were frequently associated with clumped filaments, immunoelectron microscopy showed that K10 labelling was confined to keratin filaments (including clumped filaments), and that antifilaggrin antibodies stained only keratohyalin granules, at least in the living cells. Certain keratin aggregates in the cornified cells were still devoid of filaggrin staining. However, in some cells which appeared partially cornified, filaggrin immunoreactivity occurred over the aggregated keratin filaments. Immunoblotting showed a clear increase of filaggrin/profilaggrin expression, without evidence for a qualitative abnormality. It seems unlikely, therefore, that filaggrin is primarily involved in the keratin filament clumping in EH, but that in some EH cases it interacts with keratins in a defective manner, possibly due to premature cell death and profilaggrin processing and/or altered keratin filament structure involving the interaction points of keratin with filaggrin.
    British Journal of Dermatology 11/1994; 131(6):767 - 779. DOI:10.1111/j.1365-2133.1994.tb08578.x · 3.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aggregation of tonofilaments within epidermal keratinocytes is a characteristic histologic feature of epidermolytic hyperkeratosis including the generalized form known as bullous congenital ichthyosiform erythroderma. The histologic distribution and the keratin composition of the altered tonofilaments were investigated to determine whether the aggregation was specific to any particular keratin(s). Skin samples from seven patients and one mid-trimester fetus with generalized epidermolytic hyperkeratosis, and from one patient with a localized or "nevoid" form of epidermolytic hyperkeratosis, were analyzed by using various microscopical and immunocytochemical methods. A conjunctival sample and cultured epidermal keratinocytes from one patient with generalized epidermolytic hyperkeratosis were also examined by electron microscopy and immunocytochemistry. Ultrastructurally, tonofilament aggregates were distributed within the suprabasal stratified epithelial cell layers of the epidermis, of the infundibular part of outer root sheaths, and of the sebaceous ducts and sweat ducts, selectively following the known distribution pattern of keratins K1 and K10. The abnormal tonofilaments were not found in any other cutaneous epithelia, in conjunctival epithelium, or in cultured keratinocytes, where K1 and K10 are absent or only minimally expressed. Immunoelectron microscopy showed that among the keratins detected in suprabasal epidermolytic hyperkeratosis epidermis (K1/K5/K10/K14/K16), the aggregated tonofilaments predominantly expressed K1 and K10 rather than other keratins. These results suggest that the keratin filament abnormality in epidermolytic hyperkeratosis principally involves K1 and K10 and raise the question whether epidermolytic hyperkeratosis might be primarily a disorder of one or both of these keratins.
    Journal of Investigative Dermatology 08/1992; DOI:10.1111/1523-1747.ep12611391 · 6.37 Impact Factor

Full-text (2 Sources)

Available from
May 28, 2014