Eosinophil infiltration in three patients with generalized atrophic benign epidermolysis bullosa from a Japanese family: molecular genetic and immunohistochemical studies.
Generalized atrophic benign epidermolysis bullosa (GABEB), a subtype of epidermolysis bullosa (EB), is an autosomal recessive skin disease characterized by derm-epidermal separation leading to skin fragility and atrophy and other associated abnormalities. Although a few reports demonstrated that eosinophils are infiltrating beneath bullas in infants with some types of EB, no such condition in adult GABEB patients has been known. Here we report on three adult patients with GABEB from a Japanese family, whose bullous skin lesions showed massive eosinophil infiltration. One of the three patients showed amyloid deposition at the intestine, kidney, and skin. Linkage analysis revealed that GABEB in the family was linked to COL17A1 with a maximum LOD score of 3.08. Mutation analysis identified in the three patients a homozygous insertional mutation, 209-210insCA, in exon 5 of COL17A1. The expression of mutated COL17A1 was confirmed by semiquantitative RT-PCR, but no signals for truncated COL17A1 protein were detected by the immunohistochemical studies using antibodies against BP180. Furthermore, no autoantibody against the mutant protein was detected by western blot analysis. It is thus less likely that autoantibody and/or a local immune reaction in their skin has a primary role in eosinophil infiltration in these patients.
Nomura
Masayo
M
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Hamasaki
Yoh-Ichiro
YI
Department of Dermatology, Dokkyo University School of Medicine, Tochigi, Japan.
Katayama
Ichiro
I
Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan.
Abe
Kuniko
K
Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan.
Niikawa
Norio
N
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.|CREST, Japan Science and Technology Agency (JST), Kawaguchi, Japan.
Yoshiura
Koh-Ichiro
KI
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan. kyoshi@net.nagasaki-u.ac.jp.|CREST, Japan Science and Technology Agency (JST), Kawaguchi, Japan. kyoshi@net.nagasaki-u.ac.jp.
D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology*; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008040:Genetic Linkage; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008126:Lod Score; D046529:Microscopy, Electron, Transmission; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000648:ultrastructure*
D017931:DNA Primers