A novel deletion and two recurrent substitutions on type VII collagen gene in seven Iranian patients with epidermolysis bullosa

Document Type: Original Article

Authors

1 Department of Biology, Faculty of Sciences, Guilan University, Rasht, Iran

2 Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Cellular-Molecular Research Center (CMERC), Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Objective(s): Epidermolysis bullosa is one of the most important series of mechano-bullous heritable skin disorders which is categorized into four major types according to the layer that bullae forms within basement membrane zone. In dystrophic form of the disease, blisters are made in the sublamina densa zone, at the level of type VII collagen protein which produce anchoring fibrils. Type VII collagen gene is the only responsible gene for this form. The aim of this study was to survey causative mutations of type VII collagen gene among Iranian patients with epidermolysis bullosa.
Materials and Methods: For this purpose, exons 73-75 were investigated by polymerase chain reaction followed by direct sequencing.
Results: In current study, we found three different point mutations in type VII collagen alleles in 7 out of 50 patients. Four patients were homozygous for a new deletion which resulted in frame shift (p.Pro2089fs). Two patients were homozygous for a recurrent glycine substitution (p.G2031S) and one patient was detected with an allele carrying a substitution (p.R2069C).
Conclusion: The results emphasized heterogeneity in the type VII collagen gene and will provide a sign for early diagnosis and future study of the disease pathogenesis.

Keywords


1. Fine JD. Inherited epidermolysis bullosa. Orphanet J Rare Dis 2010;5:12.

2. Burns T, Breathnach S, Cox N, Griffiths C. Rook's Textbook of Dermatology.  London: Blackwell scientific publications 2010. 2:39.1-39.32.

3. Fine JD, Bruckner-Tuderman L, Eady RA, Bauer EA, Bauer JW, Has C, et al Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 2014;70:1103-1126.

4. Chung HJ, Uitto J. Type VII collagen: the anchoring fibril protein at fault in dystrophic epidermolysis bullosa. Dermatologic clinics 2010;28:93-105.

5. Dang N, Murrell DF. Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosa. Exp Dermatol 2008;17:553-568.

6. Varki R, Sadowski S, Uitto J, Pfendner E. Epidermolysis bullosa. II. Type VII collagen mutations and phenotype–genotype correlations in the dystrophic subtypes. J Med Genet 2007;44:181-192.

7. The Human Gene Mutation Database [database on the Internet]. Cardif university. 2013.

8. Turnpenny PD, Ellard S, Emery AEH. Emery's Elements of Medical Genetics.  London: Elsevier/Churchill Livingstone 2007. 13:103-120.

9. Lin Y, Chen X-J, Liu W, Gong B, Xie J, Xiong J-H, et al. Two novel mutations on exon 8 and intron 65 of COL7A1 gene in two Chinese brothers result in recessive dystrophic epidermolysis bullosa. PLoS One 2012;7:e50579.

10. Kern JS, Kohlhase J, Bruckner-Tuderman L, Has C. Expanding the COL7A1 mutation database: novel and recurrent mutations and unusual genotype–phenotype constellations in 41 patients with dystrophic epidermolysis bullosa. J Investig Dermatol 2006;126:1006-1012.

11. Galehdari H, Mohammadian G, Azmoon S, Salehi B, Pedram M. A novel COL7A1 gene mutation in an Iranian individual suffering dystrophic epidermolysis bullosa. J Mol Diagn 2010;12:377-379.

12. Wertheim-Tysarowska K, Gos M, Niepokoj K, Kowalewski C. [Inherited skin diseases - a review  of selected genodermatoses]. Med Wieku Rozwoj 2012;16:183-195.

13. Park J, Chae H, Kim M, Kim Y, Park IY, Shin JC, et al A novel COL7A1 mutation in a Korean patient with Hallopeau-Siemens recessive dystrophic epidermolysis bullosa. Genet Mol Res 2013;12:678-682.

14. Nordal E, Mecklenbeck S, Hausser I, Skranes J, Bruckner‐Tuderman L, Gedde‐Dahl Jr T. Generalized dystrophic epidermolysis bullosa: identification of a novel, homozygous glycine substitution, G2031S, in exon 73 of COL7A1 in monozygous triplets. Br J Dermatol  2001;144:151-157.

15. Kahofer P, Bruckner-Tuderman L, Metze D, Lemmink H, Scheffer H, Smolle J. Dystrophic epidermolysis bullosa inversa with COL7A1 mutations and absence of GDA-J/F3 protein. Pediatr Dermatol 2003;20:243-248.

16. Wertheim-Tysarowska K, Sobczyńska-Tomaszewska A, Kowalewski C, Kutkowska-Kaźmierczak A, Woźniak K, Niepokój K, et al Novel and recurrent COL7A1 mutation in a Polish population. Eur J Dermatol 2012;22:23-28.

17. Pfendner EG, Nakano A, Pulkkinen L, Christiano AM, Uitto J. Prenatal diagnosis for epidermolysis bullosa: a study of 144 consecutive pregnancies at risk. Prenat Diagn 2003;23:447-456.

18. Suzuki S, Shimomura Y, Yamamoto Y, Kariya N, Shibuya M, Ito M, et al A case of recessive dystrophic epidermolysis bullosa caused by compound heterozygous mutations in the COL7A1 gene. Br J Dermatol 2006;155:838-840.