Identification and Computational Analysis of Novel Pathogenic Variants in Pakistani Families with Diverse Epidermolysis Bullosa Phenotypes
Author
Khan, Fehmida FKhan, Naima
Rehman, Sakina
Ejaz, Amir
Ali, Uzma
Erfan, Muhammad
Ahmed, Zubair M
Naeem, Muhammad
Date
2021-04-22Journal
BiomoleculesPublisher
MDPI AGType
Article
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Epidermolysis bullosa (EB) includes a group of rare gesnodermatoses that result in blistering and erosions of the skin and mucous membranes. Genetically, pathogenic variants in around 20 genes are known to alter the structural and functional integrity of intraepidermal adhesion and dermo-epidermal anchorage, leading to four different types of EB. Here we report the underlying genetic causes of EB phenotypes segregating in seven large consanguineous families, recruited from different regions of Pakistan. Whole exome sequencing, followed by segregation analysis of candidate variants through Sanger sequencing, identified eight pathogenic variants, including three novel (ITGB4: c.1285G>T, and c.3373G>A; PLEC: c.1828A>G) and five previously reported variants (COL7A1: c.6209G>A, and c.1573C>T; FERMT1: c.676insC; LAMA3: c.151insG; LAMB3: c.1705C>T). All identified variants were either absent or had very low frequencies in the control databases. Our in-silico analyses and 3-dimensional (3D) molecular modeling support the deleterious impact of these variants on the encoded proteins. Intriguingly, we report the first case of a recessively inherited form of rare EBS-Ogna associated with a homozygous variant in the PLEC gene. Our study highlights the clinical and genetic diversity of EB in the Pakistani population and expands the mutation spectrum of EB; it could also be useful for prenatal diagnosis and genetic counseling of the affected families.Identifier to cite or link to this item
http://hdl.handle.net/10713/15822ae974a485f413a2113503eed53cd6c53
10.3390/biom11050620
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