Next Generation Sequencing Identifies Double Homozygous Mutations in Two Distinct Genes (Exph5 and Col17a1) in a Patient With Concomitant Simplex and Junctional Epidermolysis Bullosa

Next Generation Sequencing Identifies Double Homozygous Mutations in Two Distinct Genes (Exph5 and Col17a1) in a Patient With Concomitant Simplex and Junctional Epidermolysis Bullosa Publisher Pubmed

Vahidnezhad H^{1, 2} ; Youssefian L^{1, 3, 4} ; Saeidian AH^{1, 4} ; Touati A^{1, 5} ; Sotoudeh S⁶ ; Jazayeri A⁷ ; Guy A⁸ ; Lovell PA⁸ ; Liu L⁸ ; Kariminejad A⁹ ; Mcgrath JA¹⁰ ; Zeinali S^{2, 11} ; Uitto J¹

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1. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
2. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
3. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
4. Genetics, Genomics and Cancer Biology PhD Program, Thomas Jefferson University, Philadelphia, PA, United States
5. Drexel University College of Medicine, Philadelphia, PA, United States
6. Department of Dermatology, Children's Medical Center, Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
7. Department of Information Science, College of Computing and Informatics, Drexel University, Philadelphia, PA, United States
8. Viapath, St Thomasâ€™ Hospital, London, United Kingdom
9. Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran
10. Institute of Dermatology, King's College London, Guy's Hospital, London, United Kingdom
11. Kawsar Human Genetics Research Center, Tehran, Iran

Source: Human Mutation Published:2018

Abstract

Epidermolysis bullosa (EB) is a heterogeneous group of heritable blistering diseases. We developed a next generation sequencing (NGS) panel covering 21 genes associated with skin fragility disorders, and it was applied to DNA from 91 probands with the diagnosis of EB. In one patient, novel homozygous mutations were disclosed in two different, unlinked EB-associated genes: EXPH5, chr11 g.108510085G > A; p.Arg1808Ter and COL17A1, chr10 g.104077423delT; p.Thr68LeufsTer106. Consequences of the COL17A1 mutation were examined by RNAseq which revealed a complex splicing pattern predicting synthesis of a truncated polypeptide (85%) or in-frame deletion of exon 4 (15% of transcripts). Transmission electron microscopy (TEM) and immunostaining revealed findings consistent with EB simplex (EBS) and junctional EB (JEB), and clinical examination revealed a complex phenotype with features of both subtypes. This case illustrates the power of next generation sequencing in identifying mutations in patients with complex EB phenotype, with implications for genotype–phenotype correlations, prenatal testing, and genetic counseling of families at risk for recurrence. © 2018 Wiley Periodicals, Inc.

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Style	Citing Format
MLA	Vahidnezhad H, et al.. "Next Generation Sequencing Identifies Double Homozygous Mutations in Two Distinct Genes (Exph5 and Col17a1) in a Patient With Concomitant Simplex and Junctional Epidermolysis Bullosa." Human Mutation, vol. 39, no. 10, 2018, pp. 1349-1354.
APA	Vahidnezhad H, Youssefian L, Saeidian AH, Touati A, Sotoudeh S, Jazayeri A, Guy A, Lovell PA, Liu L, Kariminejad A, Mcgrath JA, Zeinali S, Uitto J (2018). Next Generation Sequencing Identifies Double Homozygous Mutations in Two Distinct Genes (Exph5 and Col17a1) in a Patient With Concomitant Simplex and Junctional Epidermolysis Bullosa. Human Mutation, 39(10), 1349-1354.
Chicago	Vahidnezhad H, Youssefian L, Saeidian AH, Touati A, Sotoudeh S, Jazayeri A, Guy A, et al.. "Next Generation Sequencing Identifies Double Homozygous Mutations in Two Distinct Genes (Exph5 and Col17a1) in a Patient With Concomitant Simplex and Junctional Epidermolysis Bullosa." Human Mutation 39, no. 10 (2018): 1349-1354.
Harvard	Vahidnezhad H et al. (2018) 'Next Generation Sequencing Identifies Double Homozygous Mutations in Two Distinct Genes (Exph5 and Col17a1) in a Patient With Concomitant Simplex and Junctional Epidermolysis Bullosa', Human Mutation, 39(10), pp. 1349-1354.
Vancouver	Vahidnezhad H, Youssefian L, Saeidian AH, Touati A, Sotoudeh S, Jazayeri A, et al.. Next Generation Sequencing Identifies Double Homozygous Mutations in Two Distinct Genes (Exph5 and Col17a1) in a Patient With Concomitant Simplex and Junctional Epidermolysis Bullosa. Human Mutation. 2018;39(10):1349-1354.
BibTex	@article{ author = {Vahidnezhad H and Youssefian L and Saeidian AH and Touati A and Sotoudeh S and Jazayeri A and Guy A and Lovell PA and Liu L and Kariminejad A and Mcgrath JA and Zeinali S and Uitto J}, title = {Next Generation Sequencing Identifies Double Homozygous Mutations in Two Distinct Genes (Exph5 and Col17a1) in a Patient With Concomitant Simplex and Junctional Epidermolysis Bullosa}, journal = {Human Mutation}, volume = {39}, number = {10}, pages = {1349-1354}, year = {2018} }
RIS	TY - JOUR AU - Vahidnezhad H AU - Youssefian L AU - Saeidian AH AU - Touati A AU - Sotoudeh S AU - Jazayeri A AU - Guy A AU - Lovell PA AU - Liu L AU - Kariminejad A AU - Mcgrath JA AU - Zeinali S AU - Uitto J TI - Next Generation Sequencing Identifies Double Homozygous Mutations in Two Distinct Genes (Exph5 and Col17a1) in a Patient With Concomitant Simplex and Junctional Epidermolysis Bullosa JO - Human Mutation VL - 39 IS - 10 SP - 1349 EP - 1354 PY - 2018 ER -

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