Case of inherited epidermolysis bullosa simplex with KLHL24 gene mutation in Japan

Dear Editor, There are four subgroups of the inherited blistering disease epidermolysis bullosa (EB): epidermal bullosa simplex (EBS), junctional EB, dystrophic EB and Kindler syndrome. Although individuals with EBS have generally shown mutations in keratin 5 (KRT5) and keratin 14 (KRT14),1,2 other gene mutations have been reported. Herein, we report a Japanese case with EBS who presented the mutation of Kelchlike family member 24 (KLHL24). A female infant had been delivered by cesarean section. Immediately after birth, she presented with some blisters in frictionexposed areas, including extremities and the head with mucosal lesion (Figure 1a,b). The result of the skin biopsy specimens showed a subepidermal blister (Figure 1c) and the antigen mapping did not show a significant reduction of basement membrane zone proteins, including BP230, type XVII collagen, integrin α6/β4, plectin, laminin 332, type VII collagen, type IV collagen, KRT5, and KRT14 (Figure 1d). Electron microscopic analysis showed vesicles in the cytoplasm of basal keratinocytes, which corresponded to autolysosomes and autophagosomes (Figure 1e).2 The epidermal detachment was not evident in these studies, possibly due to the technical problems of skin biopsy. We investigated the mutations in genomic DNA from the blood samples of the case and her mother by whole exome sequencing and Sanger sequencing. We were unable to examine the father’s gene mutations. We identified a recurrent heterozygous KLHL24 mutation c.1A>G in our case. Pathogenic variants in other EBcausative genes, including KRT5/KRT14, were not detected. Her mother showed no mutation (Figure 1f). We diagnosed EBS with KLHL24 mutation. The cases with KLHL24 mutation show epidermal defects on the extremities at birth, and the defects heal with hypoand hyperpigmentation and skin atrophy, resembling burnlike scars. The skin blistering diminishes in adulthood, but fragility persists, and erosions occur after minimal mechanical trauma. Other characteristic manifestations are oral ulceration, nail thickening and onychogryphosis,