Novel keratin 5 mutation in a family with epidermolysis bullosa simplex

Gao,Jiajia; Wang,Xuebin; Zheng,Fang; Dong,Sufang; Qiu,Xueping

doi:10.3892/etm.2015.2811

Novel keratin 5 mutation in a family with epidermolysis bullosa simplex

Authors:
- Jiajia Gao
- Xuebin Wang
- Fang Zheng
- Sufang Dong
- Xueping Qiu
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Affiliations: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: October 16, 2015 https://doi.org/10.3892/etm.2015.2811
Pages: 2432-2436

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Abstract

The aim of the present study was to identify the causative gene defects associated with epidermolysis bullosa simplex (EBS) in a pedigree. The diagnosis of EBS was confirmed in two patients from that pedigree based on the clinical manifestations, histopathological examination of the skin and family history. Blood samples were collected from 6 family members and 100 heathy controls, and genomic DNA and RNA were extracted. Mutation analysis of the keratin 5 gene (KRT5) was conducted using polymerase chain reaction (PCR) direct sequencing and PCR‑restriction fragment length polymorphism. In the pedigree, the results of PCR direct sequencing revealed a heterozygous missense mutation in codon 202 of exon 2 of KRT5 (c.605T>A), which led to an amino acid change (p.L202Q) in the patients with EBS but was absent from the unaffected family members and 100 population controls. In conclusion, a novel missense mutation in the KRT5 gene was identified that had a pathogenic role in EBS in the population studied, which enriches the germline mutation spectrum of the KRT5 gene.

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1	Fine JD, Eady RA, Bauer EA, Briggaman RA, Tuderman Bruckner L, Christiano A, Heagerty A, Hintner H, Jonkman MF, McGrath J, et al: Revised classification system for inherited epidermolysis bullosa: Report of the Second International Consensus Meeting on diagnosis and classification of epidermolysis bullosa. J Am Acad Dermatol. 42:1051–1066. 2000. View Article : Google Scholar : PubMed/NCBI
2	Coulombe PA, Kerns ML and Fuchs E: Epidermolysis bullosa simplex: A paradigm for disorders of tissue fragility. J Clin Invest. 119:1784–1793. 2009. View Article : Google Scholar : PubMed/NCBI
3	Fuchs EV: The molecular biology of epidermolysis bullosa simplex. Clinical. Bauer EA, McGuire J and Moshell A: (Baltimore). Johns Hopkins University Press. 280–299. 1999.
4	Horn HM and Tidman MJ: The clinical spectrum of epidermolysis bullosa simplex. Br J Dermatol. 142:468–472. 2000. View Article : Google Scholar : PubMed/NCBI
5	Steinert PM: The two-chain coiled-coil molecule of native epidermal keratin intermediate filaments is a type I-type II heterodimer. J Biol Chem. 265:8766–8774. 1990.PubMed/NCBI
6	Soetens O, Vauloup-Fellous C, Foulon I, Dubreuil P, De Saeger B, Grangeot-Keros L and Naessens A: Evaluation of different cytomegalovirus (CMV) DNA PCR protocols for analysis of dried blood spots from consecutive cases of neonates with congenital CMV infections. J Clin Microbiol. 46:943–946. 2008. View Article : Google Scholar : PubMed/NCBI
7	Fine JD, Eady RA, Bauer EA, Bauer JW, Bruckner-Tuderman L, Heagerty A, Hintner H, Hovnanian A, Jonkman MF, Leigh I, et al: The classification of inherited epidermolysis bullosa (EB): Report of the third international consensus meeting on diagnosis and classification of EB. J Am Acad Dermatol. 58:931–950. 2008. View Article : Google Scholar : PubMed/NCBI
8	Liovic M, Stojan J, Bowden PE, Gibbs D, Vahlquist A, Lane EB and Komel R: A novel keratin 5 mutation (K5V186L) in a family with EBS-K: A conservative substitution can lead to development of different disease phenotypes. J Invest Dermatol. 116:964–969. 2001. View Article : Google Scholar : PubMed/NCBI
9	Murrell DF, Trisnowati N, Miyakis S and Paller AS: The yin and the yang of keratin amino acid substitutions and epidermolysis bullosa simplex. J Invest Dermatol. 131:1787–1790. 2011. View Article : Google Scholar : PubMed/NCBI
10	Bolling MC, Lemmink HH, Jansen GH and Jonkman MF: Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients. Br J Dermatol. 164:637–644. 2011.PubMed/NCBI
11	Smith TA, Steinert PM and Parry DA: Modeling effects of mutations in coiled-coil structures: Case study using epidermolysis bullosa simplex mutations in segment 1a of K5/K14 intermediate filaments. Proteins. 55:1043–1052. 2004. View Article : Google Scholar : PubMed/NCBI
12	Ciubotaru D, Bergman R, Baty D, Indelman M, Pfendner E, Petronius D, Moualem H, Kanaan M, Ben Amitai D, McLean WH, et al: Epidermolysis bullosa simplex in Israel: Clinical and genetic features. Arch Dermatol. 139:498–505. 2003. View Article : Google Scholar : PubMed/NCBI
13	Yasukawa K, Sawamura D, Goto M, Nakamura H, Jung SY, Kim SC and Shimizu H: Epidermolysis bullosa simplex in Japanese and Korean patients: Genetic studies in 19 cases. Br J Dermatol. 155:313–317. 2006. View Article : Google Scholar : PubMed/NCBI
14	Shinkuma S, Natsuga K, Nishie W and Shimizu H: Epidermolysis bullosa in Japan. Dermatol Clin. 28:431–432. 2010. View Article : Google Scholar : PubMed/NCBI