Detection of ATP2C1 gene mutations in a family with generalized familial benign chronic pemphigus / 中华皮肤科杂志

A 60-year-old female proband presented with recurrent erythema, blisters and erosions all over the body for 30 years, which had been aggravated 10 days prior to the presentation. Skin examination showed erythematous swelling of the bilateral eyelids with scattered dark red crusts, scattered erythema and erosions on the nasolabial folds and chin, large areas of erythema and erosions on the neck, bilateral axillae, left cubital fossa, perineum and perianal area, accompanied by bright red granulation tissues and positive Nikolsky′s sign. The proband had two sons, both of whom occasionally presented with erythema and erosions on the axillae and groin, and had not been diagnosed or treated. Blood samples were collected from the proband and her two sons, and genomic DNA was extracted and subjected to whole-exome sequencing. A heterozygous deletion mutation c.955_957del (p.A319del) was identified in the ATP2C1 gene in the proband and her two sons, which had not been previously reported. The patient was finally diagnosed with generalized familial benign chronic pemphigus.

Familial "benign" pemphigus? Erythroderma and fatal outcome

Abstract Hailey-Hailey disease, or familial benign pemphigus, is a rare bullous genodermatosis that usually presents with flaccid blisters, erosions, and maceration limited to flexural areas, resulting in increased morbidity and reduced quality of life for affected patients. The authors report an unusual case of generalized Hailey-Hailey disease with erythroderma and fatal outcome.

Tratamento da doença de Hailey-Hailey com laser de CO2 fracionado: uma série de três casos / Treatment of the Hailey-Hailey disease with fractional CO2 laser: a three-case series

A doença de Hailey-Hailey ou pênfigo familiar benigno é condição rara, que se caracteriza por lesões vesiculares e erosões, associadas a dor e queimação, que comprometem a qualidade de vida dos pacientes. Existem vários tratamentos tópicos e sistêmicos que podem promover temporariamente a remissão das lesões, não existindo tratamento curativo. Algumas opções de tratamento com resultados duradouros abrangem a dermoabrasão e a vaporização com laser de Erbium YAG ou CO2. Relatamos três casos de pacientes com lesões recorrentes e respostas limitadas aos tratamentos clássicos, que apresentaram melhora clínica importante e alívio sintomático após terapia com laser de CO2 fracionado.

The Hailey-Hailey disease or familial benign pemphigus is a rare condition, characterized by vesicular lesions and erosions with a predilection for intertriginous areas associated with pain and burning sensation that affect the quality of life of patients. There are many topical and systemic treatments for the injuries that can temporarily promote partial or complete remission, but there is no curative treatment. Some treatment options with lasting results include dermabrasion and Erbium laser resurfacing (YAG or CO2). We report three cases of patients with recurrent lesions and limited responses to classical treatments, which showed significant clinical improvement after fractional CO2 laser therapy.

Mutation analysis of ATP2C1 gene in Chinese families with Hailey-Hailey disease / 中华皮肤科杂志

Objective To detect the mutations in ATP2C1 gene in 3 Chinese Hailey-Hailey-disease (HHD) families and 1 sporadic HHD patient.Methods Three Chinese HHD families and 1 sporadic HHD patient were recruited into this study with informed consent.Blood samples were taken from the patients with HHD,unaffected individuals in the HHD families and 100 unrelated normal human controls.Genomic DNA was extracted from these blood samples.All the exons and exon-intron boundaries of the ATP2C1 gene were amplified by PCR followed by direct sequencing via dye-termination chemistry.Results Three novel missense mutations in ATP2C1 gene were identified,including a 2048 G→A mutation in exon 20 causing the substitution of arginine by lysine at position 619 in the patients from HHD family 1,853A→C mutation in exon 8 causing the substitution of threonine by proline at position 221 in the patients from family 2,and 2323T→C mutation in exon 23 causing the substitution of tyrosine by histidine at position 711.None of these mutations were found in patients from the HHD family 3,unaffected individuals from the HHD family 1 and 2,or the unrelated normal human controls.Conclusion Three novel missense mutations are identified in the ATP2C 1 gene of patients with HHD.

Tratamento da doença de Hailey-Hailey com toxina botulínica tipo A / Hailey-Hailey disease treatment with Botulinum toxin type A

Duas irmãs com doença de Hailey-Hailey, com lesões recorrentes - uma em axilas e outra em região inguinal -, e resposta limitada aos tratamentos clássicos. Elas foram tratadas com aplicação de toxina botulínica tipo A. Observamos que houve importante melhora na paciente tratada na região inguinal e remissão completa na paciente em cujas axilas sofreram tratamento. Além disso, foi possível poupar uso de antibióticos sistêmicos e corticoides tópicos. O alto custo é um fator restritivo para uso rotineiro e estudos maiores são necessários para definir eficácia e relação custo-benefício dessa intervenção.

Two sisters with recurrent lesions, one on axillae and other on the groin, and with limited response to classical treatments were treated with injections botulinum toxin type A. We observed marked improvement in the patient treated in the groin and complete remission in the patient treated in the axillae. It was possible to spare the use of systemic antibiotics and topical corticosteroids. The high cost is a restrictive factor to routine use and large studies are necessary to access efficacy and cost benefit profile.

Mutation analysis of ATP2C1 gene in patients with Hailey-Hailey disease / 中华皮肤科杂志

Objective To detect the mutations in ATP2C1 gene of 5 sporadic patients with Hailey-Hailey disease (HHD).Methods Five sporadic patients with HHD collected from the outpatient clinic setting were recruited into this study with informed consent.Blood samples were taken from all patients and 100 unrelated human controls.and DNA was extracted from these samples.Mutation scanning was carried out for ATP2C1 gene by polymerase chain reaction (PCR) and direct sequencing.Results The diagnosis of all cases was confirmed by typical clinical manifestation,cutaneous pathology and immunofluorescence pathology.Five novel mutations.including a deletion mutation (2025delG),three missence mutations (L269R,C348R,A651D) and a non-sense mutation (Q259X) were identified in these cases.No mutations were detected in any of the 100 controls.Conclusion Five novel mutations in ATP2C1 gene have been identified for Hailey-Hailey disease.

Gene Mutations in a Chinese Family with Hailey-Hailey Disease / 中华皮肤科杂志

Objective To analyse gene mutation in members of a Chinese family with Hailey-Hailey disease(HHD)and study the relationship between the genotype and clinical features of the disease.Meth-ods Genomic DNA of leucocytes were obtained from members of the Chinese family with HHD including4patients and6normal persons.Ten exons of ATP2C1gene were amplified by polymerase chain reaction(PCR)and the products were analysed by single-strand conformation polymorphism(SSCP)and direct DNA sequencing.Results A novel mutation was identified in this family.The sequence of"TGTAGCCAT"(2068→2076)was substituded by"AGATGGAACA",which caused a frame shift of open reading frame and premature termination codon(PTC)in gene ATP2C1.There was no relationship between the genotypes and the phenotypes.Conclusion Gene mutation of ATP2C1gene at exon21is the cause for HHD in this fami-ly.