Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum |
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| Affiliation: | 1. i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal;2. IBMC – Institute for Molecular and Cell Biology, Universidade do Porto, Portugal;3. Centre for Predictive and Preventive Genetics (CGPP), Universidade do Porto, Portugal;4. Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal;5. CHUC - Medical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal;6. CHULN-HSM – Serviço de Genética Médica, Centro Hospitalar Universitário de Lisboa Norte – Hospital de Santa Maria, Portugal;7. EPER – Hospital de Santo Espírito da Ilha Terceira, Portugal;8. HB - Unidade de Genética Médica, Hospital de Braga, Portugal;9. ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal;10. ICVS/3B''s, PT Government Associate Laboratory, Braga/Guimarães, Portugal;11. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;12. Centro de Psicologia, Universidade do Porto, Porto, Portugal;1. Laboratory of Molecular and Cellular Screening Processes (LPCMC), Center of Biotechnology of Sfax, University of Sfax, Tunisia;2. Medical Genetics Department, University Hedi Chaker Hospital of Sfax, Tunisia;3. Child Neurology Department, University Hedi Chaker Hospital of Sfax, Tunisia;4. Research Laboratory “Neuropédiatrie" LR19ES15, Sfax University, Tunisia;5. Radiology Department, Hedi Chaker University Hospital, University of Sfax, Sfax, Tunisia;6. Department of Ophthalmology, Habib Bourguiba Hospital, Sfax, Tunisia;7. Department of Otorhinolaryngology, University Habib Bourguiba Hospital of Sfax, Tunisia;8. Laboratory of Human Molecular Genetics, LR33ES99, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia;9. Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates;10. Human Genetics and Stem Cell Laboratory, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah, United Arab Emirates;11. Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates;1. Greenwood Genetic Center, Greenwood, SC, USA;2. Department of Pediatrics, Section of Genetics and Metabolism, Children''s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO, USA;3. Divsion of Genetics, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA;4. Dell Children''s Medical Group, Austin, TX, USA;1. Department of Neurology, Children''s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China;2. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, China;3. Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China;1. Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran;2. Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran;3. Medical Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz, Iran;1. SI Institute of Hereditary Pathology NAMS of Ukraine, Lviv, Ukraine;2. Department of Paediatrics, Medical University of Warsaw, Warsaw, Poland;3. Department of Paediatrics, Division of Propaedeutic of Paediatrics and Rare Disorders, Medical University, Wroclaw, Poland;4. Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland;5. Department of Paediatrics and Endocrinology, Medical University of Warsaw, Warsaw, Poland |
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| Abstract: | BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases. |
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| Keywords: | Dystrophic epidermolysis bullosa Genodermatosis Pathogenic variant Novel Next generation sequencing |
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