Allelic Variations of Human Keratins K4 and K5 Provide Polymorphic Markers Within the Type II Keratin Gene Cluster on Chromosome 12

Wanner, R.; Förster, Hans-Heinrich; Tilmans, I; Mischke, Dietmar

doi:10.1111/1523-1747.ep12475671

Cited by 20 publications

(13 citation statements)

References 35 publications

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“…The previously described G138E polymorphism in the H1 domain of the K5 gene which is known to result in an abnormal migration pattern of the polypeptide variant was not found in our patient. 34 Finally, sequencing of the entire rod domain of K5 did not reveal other …”

Section: Screening Of K5 Cdna For Additional Nucleotide Changesmentioning

confidence: 95%

Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex

Rugg

Rochat

et al. 1999

Eur J Hum Genet

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Epidermolysis bullosa simplex (EBS) arises from mutations within the keratin 5 and 14 (K5 and K14) genes which alter the integrity of basal keratinocytes cytoskeleton. The majority of these defects are missense mutations in the rod domain, whose locations influence the disease severity. We investigated a large family dominantly affected with the Dowling-Meara form of EBS (EBS-DM). Sequencing of amplified and cloned K5 cDNA from cultured keratinocytes revealed a 66 nucleotide deletion in one allele corresponding to the last 22 amino acid residues encoded by exon 1 (Val164 to Lys185). Sequencing of amplified genomic DNA spanning the mutant region revealed a heterozygous G-to-A transition at + 1 position of the consensus GT donor splice site of intron 1 of K5. This mutation leads to the use of an exonic GT cryptic donor splice site, located 66 nucleotides upstream from the normal donor splice site of intron 1. The corresponding peptide deletion includes the last five amino acids of the H1 head domain and the first 17 amino acids of the conserved amino terminal end of the 1A rod domain, including the first two heptad repeats and the helix initiation peptide. The shortened polypeptide is expressed in cultured keratinocytes at levels which are comparable to the normal K5 protein. This is the first splice site mutation to be reported as a cause of EBS-DM. Owing to the functional importance of the removed region, our data strongly suggest that shortened keratin polypeptide can impair keratin filament assembly in a dominant manner and causes EBS-DM.

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Section: Screening Of K5 Cdna For Additional Nucleotide Changesmentioning

confidence: 95%

Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex

Rugg

Rochat

et al. 1999

Eur J Hum Genet

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“…Multiple sequence alignment for the NA region of trichocyte keratin head domains and the H1 subdomain of cytokeratin head domains (Steinert et al, 1984Johnson et al, 1985;Franz and Franke, 1986;Knapp et al, 1986;Klinge et al, 1987;Eckert and Rorke, 1988;Fouquet et al, 1988;Semat et al, 1988;Lersch et al, 1989;Yamamoto et al, 1990;Collin et al, 1992a,b;Wanner et al, 1993;Wang et al, 1994;Takahashi et al, 1995;Roop, 1999;Whittock et al, 2000). The alignment was obtained using ClustalX 1.81 (http://www-igbmc.u-strasbg.fr/ BioInfo/, Thompson et al, 1997;Jeanmougin et al, 1998).…”

Section: Figmentioning

confidence: 99%

A Role for the 1A and L1 Rod Domain Segments in Head Domain Organization and Function of Intermediate Filaments: Structural Analysis of Trichocyte Keratin

Marekov

Steinert

Smith

2002

Journal of Structural Biology

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“…Ten micrograms of total RNA was separated on formaldehyde agarose gels and transferred to Hybond-N+ membrane (Amersham Buchler, Braunschweig, FRG) in 0.05 N NaOH for 2 h according to manufacturer's recommendation. The filters were sequentially hybridized with the following probes: the antisense oligomer P3 (5'-CTC CTT TGT TCA GCC ACA TTG GCC-3', exon 3, aa 149-157) and the antisense oligomer P3'UT [5'-GGG CTG GTC TCT GCA CAA AGA GA-3', 3' untranslated region (3'UT)] both specific for HLA-G; the antisense oligomer o-LG2-C1 specific for HLA-E [18]; a 3'UT 550 bp HLA-A-specific probe [18]; a 3'UT 450 bp HLA-B-specific probe [18]; and finally a cytokeratin K5-specific 581 bp probe containing 95 bp of 5'UTand the sequence coding for the first 165 aa amplified from cDNA with the oligomers K5-11a (5'-AGA GCC ACC TTC TGC GTC CTG C-3') and K5-llb (5'-CTG GAT GCT GGG GTC GAT TTG C-3') [19]. Oligonucleotides were labeled with terminal deoxynucleotidyl transferase (Boehringer Mannheim, Mannheim, FRG) and [a-32P] dATP (Amersham) [20].…”

Section: Northern Blot Analysismentioning

confidence: 99%

HLA‐G: expression in human keratinocytes in vitro and in human skin in vivo

et al. 1994

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Classical, polymorphic major histocompatibility complex class I molecules are expressed on most nucleated cells. They present peptides at the cell surface and, thus, enable the immune system to scan peptides for their antigenicity. The function of the other, nonclassical class I molecules in man is controversial. HLA-G which has been shown by transfection experiments to be expressed at the cell surface, is only transcribed in placental tissue and in the fetal eye. Therefore, a role of HLA-G in the control of rejection of the allogeneic fetus has been discussed. We found that HLA-G expression is induced in keratinocytes by culture in vitro. Three different alternative splicing products of HLA-G can be detected: a full length transcript, an mRNA lacking exon 3 and a transcript devoid of exon 3 and 4. Reverse transcription followed by polymerase chain reaction also revealed the presence of HLA-G mRNA in vivo in biopsies of either diseased or healthy skin.

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Allelic Variations of Human Keratins K4 and K5 Provide Polymorphic Markers Within the Type II Keratin Gene Cluster on Chromosome 12

Cited by 20 publications

References 35 publications

Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex

Donor splice site mutation in keratin 5 causes in-frame removal of 22 amino acids of H1 and 1A rod domains in Dowling-Meara epidermolysis bullosa simplex

A Role for the 1A and L1 Rod Domain Segments in Head Domain Organization and Function of Intermediate Filaments: Structural Analysis of Trichocyte Keratin

HLA‐G: expression in human keratinocytes in vitro and in human skin in vivo

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