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Neil V. Whittock, Gabrielle H. S. Ashton, Patricia J. C

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1 Striate Palmoplantar Keratoderma Resulting from Desmoplakin Haploinsufficiency 
Neil V. Whittock, Gabrielle H.S. Ashton, Patricia J.C. Dopping-Hepenstal, Matthew J. Gratian, Fiona M. Keane, Robin A.J. Eady, John A. McGrath  Journal of Investigative Dermatology  Volume 113, Issue 6, Pages (December 1999) DOI: /j x Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Clinical appearance of the hands and feet show striate and focal keratoderma. (a) On the hands there is prominent linear hyperkeratosis on the right palm extending onto the palmar aspect of the finger. On the left hand the hyperkeratosis is more diffuse. (b) On the feet there is focal keratoderma that is most prominent at trauma-prone sites. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 Electron microscopy reveals dysadhesion between keratinocytes in the mid-spinous layer. Cell–cell contact is completely absent in places, but maintained through normal desmosome-keratin filament complexes in other sites. Condensed keratin filament bundles are present in a perinuclear position. Scale bar:2.5μm. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 Structural organization of the desmoplakin gene. The gene consists of 24 exons ranging in size from 51 to 3922bp and spans ∼45kb of genomic DNA. The size of the individual exons and introns are presented in Table 2. Coding sequences are indicated by the black shading and the 5′ and 3′ untranslated regions are shown by the hatching. Numbering above denotes the exons. The position of the proband’s splice site mutation is indicated by the arrow. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 Identification of a splice-site mutation in desmoplakin I. (a) Nucleotide sequencing of the proband’s DNA reveals a heterozygous G>A transition at the donor +1 splice site of intron 7 denoted G>A. (b) This changes the consensus GT donor splice site to AT, resulting in the inclusion of all of intron 7 into the mutant mRNA, leading to a downstream premature termination codon. (c) Pedigree of the striate palmoplantar keratoderma kindred spanning three generations. Affected family members are indicated by black shading, and unaffected family members carrying the mutation are indicated by gray shading. The mutation was verified by PCR amplification of exon 7 followed by forward and reverse fluorescent sequencing. The proband (II-2) is indicated by the arrow. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

6 Figure 5 Elucidation of nucleotide sequences corresponding to the 3′-end of the human desmoplakin I cDNA. The stop codon (TAG) spanning nucleotides 8614–8616 is underlined and the putative poly adenylation signal AATAAA spanning nucleotides 9291–9296 is double-underlined. The cDNA sequence reported has been deposited in the GenBank database under accession number AF Nucleotide numbering is from the transcription start site. Journal of Investigative Dermatology  , DOI: ( /j x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

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