Genetic Linkage of the Keratin Type II Gene Cluster with Ichthyosis Bullosa of Siemens and with Autosomal Dominant Ichthyosis Exfoliativa

Steijlen, P.M.; Kremer, Hannie; Vakilzadeh, F; Happle, Rudolf; Lavrijsen, A.P.M.; Ropers, Hans‐Hilger; Mariman, E.C.M.

doi:10.1111/1523-1747.ep12394335

Cited by 31 publications

(15 citation statements)

References 23 publications

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“…The pattern of tonofilament aggregation and cytolysis in IBS is limited to the upper spinous and granular cell layers of the epidermis, 4 a distribution consistent with the known tissue expression pattern of K2e 5 . The first report of linkage to the keratin cluster on chromosome 12 6 was followed closely by simultaneous reports of mutations in the KRT2E gene, which encodes the K2e polypeptide 3,4 , 7 . One mutation, a potential methyl‐CpG deamination (1477G→A; E493K) appears to represent a disproportionate number of cases reported and probably represents a mutational hotspot in IBS 4,8 .…”

Section: Reportsupporting

confidence: 55%

A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens

Irvine

Smith

Shum

et al. 2000

Clinical and Experimental Dermatology

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Ichthyosis bullosa of Siemens (IBS; MIM: 146800) is an autosomal dominant disorder of keratinization characterized by epidermolytic hyperkeratosis without erythroderma. The clinical features are less marked than those of bullous congenital ichthyosiform erythroderma with relatively mild hyperkeratosis usually limited to the skin flexures. Mutations in the epithelial cytokeratin 2e (K2e), which is expressed in a differentiation-specific fashion in the upper spinous and granular layers of the epidermis, have been shown to cause IBS. We detected a novel mutation in a three generation kindred with IBS (1448T-->A) within exon 7 of the KRT2E gene. This is predictive of an I483N substitution in the 2B domain of K2e. This extends the range of mutations reported to date and illustrates the usefulness of molecular genetics in the diagnosis of this disorder.

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Section: Reportsupporting

confidence: 55%

A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens

Irvine

Smith

Shum

et al. 2000

Clinical and Experimental Dermatology

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“…"Mtiuserung" or tnoulting of the outer layers of their epidermis occurs, a phenotnenon not seen in EH (62). IBS was found to be linked to the type II keratin gene cluster on ehromosotne 12 (63). Again, tonofilatnent aggregation and eytolysis was seen in suprabasal cells but unlike BCIE, was confined to the upper spinous and granular layers (64), The eells affeeted in IBS closely tnirrored the exptession of a tecently characterised epidermal keratin, K2e (65), tnaking this gene a strong candidate for IBS and three groups reported tnutations simultaneously.…”

Section: K2e Mutations Eause Iehthyosis Bullosa Of Siemensmentioning

confidence: 97%

Human keratin diseases:

Corden

McLean

1996

Experimental Dermatology

202

182

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Keratins are heteropolymeric proteins which fortn the intermediate filament eytoskeleton in epithelial cells, Sinee 1991, mutations in several keratin genes have been found to cause a variety of human diseases affeeting the epidermis and other epithelial structures. Epidermolysis bullosa simplex (EBS) was the first mechanobullous disease for which the underlying genetic lesion was found, with mutations in both the K5 and K14 genes rendering basal epidermal keratinoeytes less resilient to trauma, resulting in skin fragility. The site of mutation in the keratin protein correlates with phenotypie severity in this disorder. Since tnutations were identified in the basal eell keratins, the total nutrtber of keratin genes associated with diseases has risen to eleven. The rod domains of suprabasal keratins Kl and K 10 are mutated in buUous congenital ichthyosiform erythroderma (BCIE; also ealled epidermolytic hyperkeratosis, EH) and mosaieism for Kl/KlO mutations results in a nevoid distribution of EH, An utiusual mutation in the VI domain of Kl has also been found to cause diffuse non-epidermolytie pahnoplantar keratodertna (DNEPPK), Mutations in pahnoplantar speeifie keratin K9 cause epidertnolytic pahnoplantar keratoderma (EPPK) and mutations in the late differentiation suprabasal keratin l<.2e cause iehthyosis tiullosa of Siemens (IBS). In the last year or so, mutations were discovered in differentiation speeifie keratins K6a and K16 eausing pachyonychia eongenita type 1 and KI 7 mutations occur in pachyonychia eongenita type 2, K16 and K17 mutations have also been reported to produee phenotypes with little or no nail changes: K16 tnutations can present as focal non-epidermolytic pahnoplantar keratodertna (NEPPK) and K17 mutations can result in a phenotype resembling steatoeystoma multiplex, Reeently, mutation of mueosal keratin pair K4 and K13 has been shown to underlie white sponge nevus (WSN), This year, the ftrst mutations in a keratin-associated protein, plectin, were shown to cause a variant of epidertnolysis bullosa associated with late-onset muscular dystrophy (MD-EBS), An unusual mutation has been identified in K5 which is responsible for EBS with mottled pigmentation and genetic linkage analysis suggests that the hair disorder monilethrix is likely to be due to a tnutation in a hair keratin. The study of keratin diseases has led to a better understanditig of the itnportanee of the intermediate filament cytoskeletoti and associated cotinector tnolecules iti tnaintaining the structural integrity of the epidermis and other high stress epithelial tissues, as well as allowing diagnosis at the molecular level thus facilitating prenatal testing for this heterogeneous group of genodertnatoses.

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“…2). The first report of linkage to the keratin cluster on chromosome 12 77 was followed by three simultaneous reports of mutations in K2e. Rothnagel et al .…”

Section: Ichthyosis Bullosa Of Siemensmentioning

confidence: 99%

Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation

Irvine

McLean

1999

British Journal of Dermatology

379

326

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Keratins are obligate heterodimer proteins that form the intermediate filament cytoskeleton of all epithelial cells. Keratins are tissue and differentiation specific and are expressed in pairs of types I and II proteins. The spectrum of inherited human keratin diseases has steadily increased since the causative role of mutations in the basal keratinocyte keratins 5 and 14 in epidermolysis bullosa simplex (EBS) was first reported in 1991. At the time of writing, mutations in 15 epithelial keratins and two trichocyte keratins have been associated with human diseases which include EBS, bullous congenital ichthyosiform erythroderma, epidermolytic palmoplantar keratoderma, ichthyosis bullosa of Siemens, diffuse and focal non-epidermolytic palmoplantar keratoderma, pachyonychia congenita and monilethrix. Mutations in extracutaneous keratins have been reported in oral white sponge naevus and Meesmann's corneal dystrophy. New subtleties of phenotype-genotype correlation are emerging within the keratin diseases with widely varying clinical presentations attributable to similar mutations within the same keratin. Mutations in keratin-associated proteins have recently been reported for the first time. This article reviews clinical, ultrastructural and molecular aspects of all the keratin diseases described to date and delineates potential future areas of research in this field.

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Genetic Linkage of the Keratin Type II Gene Cluster with Ichthyosis Bullosa of Siemens and with Autosomal Dominant Ichthyosis Exfoliativa

Cited by 31 publications

References 23 publications

A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens

A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens

Human keratin diseases:

Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation

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