Figure 1.

Pedigree and Skin Pathology in This Autosomal-Recessive Skin Fragility Disorder

(A) The family pedigree. Squares denote male family members, and circles female family members; filled-in symbols indicate clinically affected individuals.

(B) Affected individual II-2 with skin crusting at the site of a recent trauma-induced erosion.

(C) Higher magnification of the crusted erosion. Additional clinical images are shown in Figure S1.

(D) Light microscopy of skin sampled from the upper arm reveals mild acanthosis and hyperkeratosis as well as a ruffled appearance to the dermal-epidermal junction (Richardson's stain; scale bar represents 50 μm).

(E) Low-magnification transmission electron micrograph shows widening of spaces between keratinocytes in the lower epidermis with some aggregation of keratin filaments (scale bar represents 3 μm).

(F) Higher-magnification transmission electron micrograph reveals keratin filament disruption (blue arrow) as well as perinuclear accumulation of vesicles (green arrow) (scale bar represents 0.5 μm).

(G) There is also focal accumulation of vesicles close to the plasma membrane (green arrow) (scale bar represents 0.25 μm).