1. Compound Heterozygosity for Non-Sense and Mis-Sense Mutations in Desmoplakin Underlies Skin Fragility/Woolly Hair Syndrome 
Neil V. Whittock, Hong Wan, Robin A.J. Eady 
Journal of Investigative Dermatology 
Volume 118, Issue 2, Pages (February 2002)
DOI: /j x x
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

2. Figure 1
Clinical appearance of the skin fragility/woolly hair syndrome proband B. At birth the patient developed blistering of the heels (a) and the lower limbs (b). At the age of 4 y old the patient showed signs of hyperkeratosis on the soles (c) with nail dystrophy (d). At 17 y old the patient has developed severe hyperkeratosis of the plantar aspects of the foot (e) with worsening nail dystrophy (f). Hyperkeratosis is developing over the palms (g) and the hair is woolly and receding (h).
Journal of Investigative Dermatology  , DOI: ( /j x x)
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

3. Figure 2
Immunofluorescence microscopy analysis of palmoplantar epidermis for proband A. Desmoplakin labeling (NW6) in (a) epidermis from an affected individual and (b) unaffected epidermis. Note that desmoplakin immunofluorescence in (a) is punctate at sites of cell–cell contact as well as cytoplasmic, whereas (b) shows the characteristic intercellular staining. Plakoglobin labeling in (c) affected epidermis shows a more normal distribution although some punctate staining is seen. Plakophilin 1 labeling in (d) affected epidermis shows the normal intercellular appearance. Scale bar: 50 µm.
Journal of Investigative Dermatology  , DOI: ( /j x x)
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

4. Figure 3
Electron microscopy analysis of palmoplantar epidermis for proband A. Electron microscopy reveals (a) dysadhesion between keratinocytes of the suprabasal layers. Cell–cell contact is completely absent in some places, with small desmosomes in others. There are areas containing (b) desmosomes that have been pulled away from their cells. The area boxed in (b) is shown in higher magnification in (c). Scale bars: (a) 3 µm; (b) 0.8 µm; (c) 0.2 µm.
Journal of Investigative Dermatology  , DOI: ( /j x x)
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

5. Figure 4
Characterization of the desmoplakin mutations and demonstration of haploinsufficiency at the transcript level. Nucleotide sequencing of the probands DNA reveals the heterozygous substitutions 2427T > A (C809X) and 861T > G (N287K) for case A, and the heterozygous substitutions 1990C > T (Q664X) and 7096C > T (R2366C) for case B (indicated by arrows). Nucleotide sequencing of the probands cDNA reveals homozygosity at these nucleotide positions, thus, demonstrating haploinsufficiency due to non-sense-mediated mRNA decay.
Journal of Investigative Dermatology  , DOI: ( /j x x)
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

6. Figure 5
Inheritance pattern and position of the desmoplakin mutations. (a) Nucleotide sequencing of the family members demonstrated an autosomal recessive inheritance pattern. (b) Position of the non-sense and mis-sense mutations within the desmoplakin protein for cases A and B. Amino terminal NN, Z, Y, X, W, V, and carboxy terminals A, B, and C designations according to (Green et al, 1992).
Journal of Investigative Dermatology  , DOI: ( /j x x)
Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions