Advantages of whole-exome sequencing over immunomapping in 67 Brazilian patients with epidermolysis bullosa

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Samantha Vernaschi Kelmann ^[1] ; Bruno de Oliveira Stephan ^[2] ; Silvia Maria de Macedo Barbosa ^[3] ; Rita Tiziana Verardo Polastrini ^[4] ; Zilda Najjar Prado de Oliveira ^[5] ; Maria Cecília Rivitti-Machado ^[6] ; Gustavo Marquezani Spolador ^[7] ; Rachel Sayuri Honjo ^[8] ; Ken Saida ^[9] ; Naomichi Matsumoto ^[10] ; Chong Ae Kim ^[11]

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^[1] Universidade de São Paulo. Faculty of Medicine. Genetics Unit, Instituto da Criança, Hospital das Clínicas - Brasil

^[2] Universidade de São Paulo. Faculty of Medicine. Genetics Unit, Instituto da Criança, Hospital das Clínicas - Brasil

^[3] Universidade de São Paulo. Faculty of Medicine. Pain and Palliative Care Unit, Instituto da Criança, Hospital das Clínicas - Brasil

^[4] Universidade de São Paulo. Faculty of Medicine. Pain and Palliative Care Unit, Instituto da Criança, Hospital das Clínicas - Brasil

^[5] Universidade de Sao Paulo. Faculty of Medicine. Department of Dermatology, Hospital das Clinicas - Brasil

^[6] Universidade de Sao Paulo. Faculty of Medicine. Department of Dermatology, Hospital das Clinicas - Brasil

^[7] Universidade de São Paulo. Faculty of Medicine. Genetics Unit, Instituto da Criança, Hospital das Clínicas - Brasil

^[8] Universidade de São Paulo. Faculty of Medicine. Genetics Unit, Instituto da Criança, Hospital das Clínicas - Brasil

^[9] Yokohama City University. Graduate School of Medicine Yokohama. Department of Human Genetics - Japão

^[10] Yokohama City University. Graduate School of Medicine Yokohama. Department of Human Genetics - Japão

^[11] Universidade de São Paulo. Faculty of Medicine. Genetics Unit, Instituto da Criança, Hospital das Clínicas - Brasil

• Tipo de documento: Artigo Científico
• Fonte: ANAIS BRASILEIROS DE DERMATOLOGIA; v. 99, n. 3, p. 350-356, 2024-05-31.

Resumo

Abstract Background Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involves a skin biopsy. Most recently, whole exome sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. Objective To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. Methods Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing from skin biopsies. Results 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS), and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1 associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the results were concordant with exome results in 37 (62%), discordant in 13 (22%), and inconclusive in 9 patients (15%). Study limitations Even though EB is a rare disease, for statistical purposes, the number of patients evaluated by this cohort can still be considered limited; other than that, there was a significant difference between the proportion of types of EB (only one case with JEB, against more than 50 with DEB), which unfortunately represents a selection bias. Also, for a small subset of families, segregation (usually through Sanger sequencing) was not an option, usually due to deceased or unknown parent status (mostly the father). Conclusion Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in about 1/3 of the patients. This study shows that WES is an effective method for the diagnosis and genetic counseling of EB patients. (AU)

• Processo FAPESP: 19/21644-0 - Impacto de variantes genéticas na estabilidade do genoma e seus efeitos no fenótipo
• Beneficiário: Maria Isabel de Souza Aranha Melaragno
• Modalidade de apoio: Auxílio à Pesquisa - Temático