Genotype–Phenotype Correlations of Dystrophic Epidermolysis Bullosa in India: Experience from a Tertiary Care Centre

Abstract

Recent advances in the field of genomics have seen the successful implementation of whole exome sequencing as a rapid and efficient diagnostic strategy in several genodermatoses. The aim of this study was to explore the potential of molecular studies in dystrophic epidermolysis bullosa (DEB) in India. Whole exome sequencing was performed using genomic DNA from each case of epidermolysis bullosa, followed by massively parallel sequencing. Resulting reads were mapped to the human reference genome hg19. Sanger sequencing subsequently confirmed the potentially pathogenic mutations. Whole exome sequencing of 18 patients with DEB from 17 unrelated Indian families revealed 20 distinct sequence variants in the COL7A1 gene including 2 widely prevalent mutations. Dominant inheritance was seen in 7 patients, while 11 patients showed a highly variable recessive DEB. This preliminary study using exome sequencing is clearly encouraging and will serve as the basis for future large-scale molecular studies to actively identify and understand DEB in the Indian population.

Inherited epidermolysis bullosa: update on the clinical and genetic aspects

“…From the development of new generation sequencing technologies, new studies, including large sample numbers, have enabled the establishment of genotype-phenotype correlations for the disease. 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 The main subtypes of DEB are detailed below.…”

“… 7 It should be noted, however, that several other types of variants, in different combinations, have also been associated with this subtype. 67 , 79 , 81 , 82 , 83 , 84 The intermediate form is characterized the presence of at least one variant that allows for some type VII collagen production, thus enabling the assembly, even if partial, of the anchoring fibrils. Thus, the genetic changes associated with this subtype can affect the association of polypeptides, the formation and stability of the triple helix, or cause some conformational modification in the protein.…”

Genomics of rare genetic diseases—experiences from India

“…A large number of cases have been solved through the GUaRDIAN program, and a subset of interesting investigations have been published in peer-reviewed journals, which encompass diseases as diverse as epidermolysis bullosa [140–143], familial Mediterranean fever [144], lamellar ichthyosis [145], sporadic acrokeratosis verruciformis [146], rare syndromes of mineralocorticoid excess [147], severe combined immunodeficiency [148], X-linked agammaglobulinemia [149], hyper IgE syndrome [150], Dowling-Degos disease [151], and megalencephalic leukoencephalopathy [152], to list a few. Furthermore, GUaRDIAN is actively investigating the genetic conundrum in Indian rare disease cohorts conforming to cardiology, neurology, dermatology, primary immunodeficiency, endocrinology, nephrology, mitochondrial disorders, and lysosomal storage disorders, among others.…”

“…JEB was studied in a small cohort of six patients from four consanguineous families with a wide range of clinical variability, identifying variations in the genes laminin subunit alpha 3 (LAMA3) , laminin subunit β3 (LAMB3) , collagen type XVII α1 (COL17A1) [142]. In the case of DEB, 18 patients from 17 unrelated families were studied and 20 distinct variations were found in COL7A1 gene [143]. There have also been other reports which discovered novel variants that expanded the known mutation spectrum of EB [141, 154].…”

Novel and very rare causative variants in the COL7A1 gene of Vietnamese patients with recessive dystrophic epidermolysis bullosa revealed by whole‐exome sequencing

“…In 2015, the pathogenic mutation identification of nine EB patients, failed by skin biopsy analysis and Sanger sequencing, was performed successfully by WES (Takeichi et al, 2015). The implementation of WES as a diagnostic tool in EB was referred to in several published studies to this point (Gong, Liu, Li, & Xu, 2019; Mahajan et al, 2018; Yenamandra et al, 2017, 2018).…”