Intractable Rare Dis Res. 2021;10(2):88-94. (DOI: 10.5582/irdr.2020.03150)
Novel mutations of epidermolysis bullosa identified using wholeexome sequencing in Indonesian Javanese patients
Widhiati S, Danarti R, Trisnowati N, Purnomosari D, Wibawa T, Soebono H
Epidermolysis bullosa (EB) is a group of inherited blistering skin diseases known to have heterogenicity of phenotypes and genotypes. There are four main types of EB: simplex, junctional, dystrophic, and Kindler syndrome, which are further classified into 34 distinct subtypes. Twenty different gene mutations are responsible for the loss of function and integrity of the basal membrane zone. In limited-resource settings such as Indonesia, diagnoses of hereditary skin disease often rely on clinical features. This limitation was managed by using the Clinical Diagnostic Matrix EB for clinical diagnosis support and whole-exome sequencing for genetic analysis. This study is the first wholeexome sequencing analysis of Javanese Indonesian patients with EB. The genetic analysis from four patients with EB identified all novel mutations unreported in the dbSNP database. There are Kindler syndrome with FERMT1 frameshift mutation in exon 4, at c.388A (p.I130fs), which causes truncated protein; junctional EB generalized intermediate (JEB-GI) subtype with missense mutation at LAMB3 gene position c.A962C (p.H321P); and recessive dystrophic EB (RDEB) a missense mutation at COL7A1 gene position c.G5000T (p.G1667V). The whole-exome sequencing was further verified by Sanger sequencing. The new mutations' finding is possibly due to the limited genetic database in the Malayo-Polynesian ethnic group. Indonesia has hundreds of ethnic groups, and the Javanese is the largest ethnic group that populates Indonesia. Genetic data of these ethnic groups is important to be established in the international genetic database. This combination of clinical diagnostic and genetic analysis tools with whole-exome sequencing confirmed the challenging diagnosis of epidermolysis bullosa.