Self‐improving dystrophic epidermolysis bullosa: First report of clinical, molecular, and genetic characterization of five patients from Southeast Asia

Bishnoi, Priya; Ng, Yi Zhen; Wei, Heming; Tan, Ene‐Choo; Lunny, Declan P.; Wong, Xuan Fei Colin Cornelius; Fon, Leong Kin; Gondokaryono, Srie Prihianti; Diana, Inne Arline; Common, John E.A.; Koh, Mark Jean Aan; Lane, E. Birgitte

doi:10.1002/ajmg.a.61975

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…However, two studies reported two Sundanese Indonesian families with dystrophic EB. They reported the mutations in COL7A1 at c.6218G>A; pGly2073Asp, c.5945G.T; pGly1982Val and c.6253G>T; p.Gly2085Trp (25,26). We did not find other articles associated with EB genetic examination in Indonesian traits.…”

Section: Resultscontrasting

confidence: 56%

Novel mutations of epidermolysis bullosa identified using whole-exome sequencing in Indonesian Javanese patients

Widhiati

Danarti

Trisnowati

et al. 2021

IRDR

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clinical diagnostic matrix, Kindler syndrome, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, Malayo-Polynesian ethnic group 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.

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Section: Resultscontrasting

confidence: 56%

Novel mutations of epidermolysis bullosa identified using whole-exome sequencing in Indonesian Javanese patients

Widhiati

Danarti

Trisnowati

et al. 2021

IRDR

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Section: Discussionmentioning

confidence: 99%

“…A handful of EB cases have been reported in Southeast Asian populations including Thai, Malaysian, Singaporean, and Indonesian (Singalavanija et al, 1994;Wessagowit et al, 2007;Tang et al, 2013;Bishnoi et al, 2021) with only two studies providing molecular data limited to COL7A1. (Wessagowit et al, 2007;Bishnoi et al, 2021). One likely reason for the small number of reports on EB with its type/subtype diagnosis in Thailand, at least, is the lack of availability of sophisticated immunohistopathological analyses specific for the disorder.…”

Section: Discussionmentioning

confidence: 99%

Epidermolysis Bullosa With Congenital Absence of Skin: Congenital Corneal Cloudiness and Esophagogastric Obstruction Including Extended Genotypic Spectrum of PLEC, LAMC2, ITGB4 and COL7A1

et al. 2022

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Epidermolysis bullosa (EB) is a rare and genetically heterogeneous disorder characterized by skin fragility and blister formation occurring spontaneously or after minor trauma. EB is accompanied by congenital absence of skin (EB with CAS) in some patients. Pathogenic variants of COL7A1 are responsible for EB with CAS in the vast majority of cases. Type and subtype diagnosis of EB with CAS generally requires specific immunohistological examinations that are not widely available plus targeted gene analysis. The present study aimed to determine the clinical features of five patients affected by EB with CAS and to identify the underlying genetic defects using whole exome sequencing (WES) followed by focused analysis of the target genes. Four patients had generalized skin involvement and one had localized defects. Two patients exhibited extremely severe skin manifestations and congenital cloudy cornea along with pyloric atresia, and one had partial esophagogastric obstruction and anuria due to vesicoureteric obstruction. In the WES analysis, the average coverage of the target exons was 99.05% (726 of 733 exons), with a range of 96.4–100% for individual genes. We identified four novel and two known pathogenic/likely pathogenic variants of five distinct genes in the examined families: PLEC:c.2536G > T (p.Glu846Ter); LAMC2:c.3385C > T (p.Arg1129Ter); KRT5:c.429G > A (p.Glu477Lys); ITGB4:c.794dupC (p.Ala266SerfsTer5); COL7A1:c.5440C > T (p.Arg1814Cys); and COL7A1:c.6103delG. All alleles were inherited from the parents, except for the KRT5 variant as a de novo finding. The findings reveal extremely rare phenotypes found in EB with CAS, namely congenital cloudy cornea, esophagogastric obstruction, and anuria, and extend the genotypic spectrum of EB-related genes. The data confirm that WES provides very high coverage of coding exons/genes and support its use as a reasonable alternative method for diagnosis of EB. The present data from an underrepresented population in Southeast Asia could further broaden the knowledge and research on EB.

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Self‐improving dystrophic epidermolysis bullosa with a novel heterozygous missense variant in the COL7A1 gene in a Taiwanese family

Tsai,

Tu,

et al. 2024

Wound Repair Regeneration

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Self‐improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self‐improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self‐improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases.

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Self‐improving dystrophic epidermolysis bullosa: First report of clinical, molecular, and genetic characterization of five patients from Southeast Asia

Cited by 3 publications

References 15 publications

Novel mutations of epidermolysis bullosa identified using whole-exome sequencing in Indonesian Javanese patients

Novel mutations of epidermolysis bullosa identified using whole-exome sequencing in Indonesian Javanese patients

Epidermolysis Bullosa With Congenital Absence of Skin: Congenital Corneal Cloudiness and Esophagogastric Obstruction Including Extended Genotypic Spectrum of PLEC, LAMC2, ITGB4 and COL7A1

Self‐improving dystrophic epidermolysis bullosa with a novel heterozygous missense variant in the COL7A1 gene in a Taiwanese family

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