Widhiati Suci, Danarti Retno, Trisnowati Niken, Purnomosari Dewajani, Wibawa Tri, Soebono Hardyanto
Department of Dermatology and Venereology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia.
Doctoral Study Program, Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada, Yogyakarta, Indonesia.
Intractable Rare Dis Res. 2021 May;10(2):88-94. doi: 10.5582/irdr.2020.03150.
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 whole-exome 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 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 gene position c.A962C (p.H321P); and recessive dystrophic EB (RDEB) a missense mutation at 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.
大疱性表皮松解症（EB）是一组遗传性水疱性皮肤病，已知其表型和基因型具有异质性。EB主要有四种类型：单纯型、交界型、营养不良型和Kindler综合征，它们又进一步分为34个不同的亚型。20种不同的基因突变导致基底膜带功能和完整性丧失。在印度尼西亚等资源有限的地区，遗传性皮肤病的诊断往往依赖于临床特征。通过使用EB临床诊断矩阵来支持临床诊断，并进行全外显子组测序进行基因分析，解决了这一局限性。本研究是对印度尼西亚爪哇族EB患者进行的首次全外显子组测序分析。对4例EB患者的基因分析确定了所有在dbSNP数据库中未报告的新突变。其中有Kindler综合征，外显子4发生移码突变，位于c.388A（p.I130fs），导致蛋白质截短；交界型EB泛发性中间型（JEB-GI）亚型，基因位置c.A962C（p.H321P）发生错义突变；隐性营养不良型EB（RDEB），基因位置c.G5000T（p.G1667V）发生错义突变。全外显子组测序通过桑格测序进一步验证。新突变的发现可能是由于马来-波利尼西亚族群的基因数据库有限。印度尼西亚有数百个民族，爪哇族是印度尼西亚人口最多的民族。这些民族的基因数据对于建立国际基因数据库很重要。临床诊断和基因分析工具与全外显子组测序相结合，证实了大疱性表皮松解症诊断的挑战性。
