Figures
Figure 1
Clinical and pathological features and ATP2C1 mutation analysis in the present patient with Hailey-Hailey disease (HHD). A ) Recurrent erosive erythema is seen on the groin. B ) A longitudinal, linear ulcer (arrow) in the lower oesophagus is recognised by endoscopy. C ) A biopsy specimen from the skin lesion on the groin reveals acantholysis and dyskeratosis in the suprabasal layers of the epidermis, the so called “dilapidated brick wall”. Only limited inflammatory cell infiltration is observed. D -E ) Biopsy specimens from the oesophageal lesion show acantholytic squamous epithelium histologically. Dyskeratosis is seen in the epithelium, but neither corps ronds nor grains are observed (arrows; dyskeratotic cells) (D ). Only limited inflammatory cell infiltration is observed in the epithelium (E ). F) The mutation c.423T>A (at the 5’ end of exon 7), detected by whole-exome sequencing, was confirmed by Sanger sequencing analysis of ATP2C1 based on the patient's genomic DNA from peripheral blood leukocytes. G ) ATP2C1 mRNA fragments derived from exon 5-9 of the patient's mutant and wild-type alleles. Red arrows indicate the position of the RT-PCR primers (ATP2C1_ex5mRNA_65(MK).f 5’-TTATCGTTGTTACAGTTGCCTTTGTTCA-3’ and ATP2C1_ex9mRNA_65(MK).r 5’-TTTCTCCTGTTCCAATGACAACACC-3’). Most of the mRNA derived from the mutant allele escaped nonsense-mediated mRNA decay (NMD), because the nucleotides A and T at position 423 were present in roughly equal amounts. A sufficient amount of the truncated protein is thought to have been produced in the present case. H) Agarose gel electrophoresis of RT-PCR products derived from the fragment between exons 5 and 9 of ATP2C1 using mRNA from whole blood of the patient as a template. The specific primers ATP2C1_ex5mRNA_65(MK).f and ATP2C1_ex9mRNA_65(MK).r were used. The RT-PCR product from the patient shows only a 381-bp band (a normally spliced fragment). No aberrantly spliced fragment derived from the mutant allele with c.423T>A was detected. A chromatograph of the Sanger sequencing analysis for the RT-PCR product is shown in (G ). I) A schematic model of the domain structure of SPCA1; green areas indicate transmembrane domains (from M1 to M10) and the mutation site is marked by a red arrow.
Figure 1
Authors
1 Department of Dermatology, Nagoya University Graduate School of Medicine,
2 Department of Dermatology, Japan Community Health Care Organization Chukyo Hospital,
3 Department of Gastroenterological Medicine, Japan Community Health Care Organization Chukyo Hospital,
4 Department of Genetics, Research Institute of Environmental Medicine, Nagoya University,
5 Department of Human Genetics and Molecular Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Hailey-Hailey disease (HHD) is an autosomal dominant disease characterized by acantholysis and is caused by ATP2C1 mutations[1]. Here, we report the first case of HHD with an oesophageal lesion in which the diagnosis was confirmed by gene analysis.A 79-year-old Japanese male had had repetitive erosions in the groin since his late twenties (figure 1A). The erosions had exacerbated every summer. His son also had similar skin lesions. A lesion on the groin revealed acantholysis and dyskeratosis in the [...]