Mutational analysis of epidermolysis bullosa in Taiwan by whole-exome sequencing complemented by RNA sequencing: a series of 77 patients.
Orphanet J Rare Dis
; 17(1): 451, 2022 12 28.
Article
em En
| MEDLINE
| ID: mdl-36578049
ABSTRACT
BACKGROUND:
Epidermolysis bullosa (EB) is a heterogeneous group of hereditary skin diseases characterized by skin fragility. Primary data on Taiwanese population remain scarce.METHODS:
We gathered clinical information from EB patients at National Cheng Kung University Hospital from January, 2012, to June, 2021. Diagnostic tests including transmission electron microscopy, immunofluorescence studies, and whole-exome sequencing (WES) were performed. The pathogenicity of novel splice-site mutations was determined through reverse transcriptase-PCR of skin mRNA followed by Sanger and/or RNA sequencing.RESULTS:
Seventy-seven EB patients from 45 families were included 19 EB simplex, six junctional EB, and 52 dystrophic EB. Pathogenic variants were identified in 37 of 38 families (97.4%), in which WES was used as a first-line tool for mutational analysis; RNA sequencing determined pathogenic variants in the remaining one family. A total of 60 mutations in EB-related genes were identified, including 22 novel mutations. The mutations involved KRT5, KRT14, PLEC, COL17A1, LAMB3, LAMA3, ITGB4, and COL7A1. Over one-quarter of DEB patients had EB pruriginosa.CONCLUSIONS:
The distinct clinical presentation and molecular pathology of EB in Taiwan expand our understanding of this disorder. WES was an effective first-line diagnostic tool for identifying EB-associated variants. RNA sequencing complemented WES when multiple potentially pathogenic splice-site mutations were found.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epidermólise Bolhosa Distrófica
/
Epidermólise Bolhosa
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article