High frequency of the 425A → G splice-site mutation and novel mutations of the COL7A1 gene in central Europe: Significance for future mutation detection strategies in dystrophic epidermolysis bullosa

M. Csikós, H. I. Szocs, A. Lászik, S. Mecklenbeck, A. Horváth, S. Kárpáti, L. Bruckner-Tuderman

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Mutations in the type VII collagen gene (COL7A1) are responsible for dominant and recessive forms of dystrophic epidermolysis bullosa (DEB). These mutations are usually specific for individual families; only a few cases of recurring mutations have been identified. Objectives: Forty-three unrelated Hungarian and German patients with different DEB phenotypes were screened for novel and recurrent COL7A1 mutations. Methods: All patients were classified based on clinical and genetic findings, skin immunofluorescent antigen mapping, and electron microscopic studies. Mutation analysis was performed by amplification of genomic DNA with polymerase chain reaction using COL7A1-specific primers, heteroduplex analysis, and direct nucleotide sequencing. Restriction endonuclease digestion was used for family screening and mutation verification. Results: In this group of patients, the splice-site mutation 425A → G was observed frequently, in 11 of 86 alleles (12-8%), once in homozygous form and in nine cases in heterozygous form. One of 100 control alleles from clinically unaffected individuals also carried the mutation. We also identified three novel mutations: the 976-3C → A splice-site mutation, and the 4929delT and 8441-15del20 deletions. Conclusions: High recurrence of the splice-site mutation 425A → G in central European patients with DEB should be taken into account when designing COL7A1 mutation detection strategies. Reporting of three novel COL7A1 mutations in this study further emphasizes the molecular heterogeneity of DEB and provides more information for studies on genotype-phenotype correlations in different DEB subtypes.

Original languageEnglish
Pages (from-to)879-886
Number of pages8
JournalBritish Journal of Dermatology
Volume152
Issue number5
DOIs
Publication statusPublished - May 2005

Fingerprint

Epidermolysis Bullosa Dystrophica
Mutation
Genes
Collagen Type VII
Alleles
Heteroduplex Analysis
DNA Restriction Enzymes
Genetic Association Studies
DNA-Directed DNA Polymerase

Keywords

  • COL7A1
  • Dystrophic epidermolysis bullosa
  • Genotype-phenotype
  • Recurrent mutation
  • Type VII collagen

ASJC Scopus subject areas

  • Dermatology

Cite this

@article{a6e558e18f5849d7b39a93e228232470,
title = "High frequency of the 425A → G splice-site mutation and novel mutations of the COL7A1 gene in central Europe: Significance for future mutation detection strategies in dystrophic epidermolysis bullosa",
abstract = "Background: Mutations in the type VII collagen gene (COL7A1) are responsible for dominant and recessive forms of dystrophic epidermolysis bullosa (DEB). These mutations are usually specific for individual families; only a few cases of recurring mutations have been identified. Objectives: Forty-three unrelated Hungarian and German patients with different DEB phenotypes were screened for novel and recurrent COL7A1 mutations. Methods: All patients were classified based on clinical and genetic findings, skin immunofluorescent antigen mapping, and electron microscopic studies. Mutation analysis was performed by amplification of genomic DNA with polymerase chain reaction using COL7A1-specific primers, heteroduplex analysis, and direct nucleotide sequencing. Restriction endonuclease digestion was used for family screening and mutation verification. Results: In this group of patients, the splice-site mutation 425A → G was observed frequently, in 11 of 86 alleles (12-8{\%}), once in homozygous form and in nine cases in heterozygous form. One of 100 control alleles from clinically unaffected individuals also carried the mutation. We also identified three novel mutations: the 976-3C → A splice-site mutation, and the 4929delT and 8441-15del20 deletions. Conclusions: High recurrence of the splice-site mutation 425A → G in central European patients with DEB should be taken into account when designing COL7A1 mutation detection strategies. Reporting of three novel COL7A1 mutations in this study further emphasizes the molecular heterogeneity of DEB and provides more information for studies on genotype-phenotype correlations in different DEB subtypes.",
keywords = "COL7A1, Dystrophic epidermolysis bullosa, Genotype-phenotype, Recurrent mutation, Type VII collagen",
author = "M. Csik{\'o}s and Szocs, {H. I.} and A. L{\'a}szik and S. Mecklenbeck and A. Horv{\'a}th and S. K{\'a}rp{\'a}ti and L. Bruckner-Tuderman",
year = "2005",
month = "5",
doi = "10.1111/j.1365-2133.2005.06542.x",
language = "English",
volume = "152",
pages = "879--886",
journal = "British Journal of Dermatology",
issn = "0007-0963",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - High frequency of the 425A → G splice-site mutation and novel mutations of the COL7A1 gene in central Europe

T2 - Significance for future mutation detection strategies in dystrophic epidermolysis bullosa

AU - Csikós, M.

AU - Szocs, H. I.

AU - Lászik, A.

AU - Mecklenbeck, S.

AU - Horváth, A.

AU - Kárpáti, S.

AU - Bruckner-Tuderman, L.

PY - 2005/5

Y1 - 2005/5

N2 - Background: Mutations in the type VII collagen gene (COL7A1) are responsible for dominant and recessive forms of dystrophic epidermolysis bullosa (DEB). These mutations are usually specific for individual families; only a few cases of recurring mutations have been identified. Objectives: Forty-three unrelated Hungarian and German patients with different DEB phenotypes were screened for novel and recurrent COL7A1 mutations. Methods: All patients were classified based on clinical and genetic findings, skin immunofluorescent antigen mapping, and electron microscopic studies. Mutation analysis was performed by amplification of genomic DNA with polymerase chain reaction using COL7A1-specific primers, heteroduplex analysis, and direct nucleotide sequencing. Restriction endonuclease digestion was used for family screening and mutation verification. Results: In this group of patients, the splice-site mutation 425A → G was observed frequently, in 11 of 86 alleles (12-8%), once in homozygous form and in nine cases in heterozygous form. One of 100 control alleles from clinically unaffected individuals also carried the mutation. We also identified three novel mutations: the 976-3C → A splice-site mutation, and the 4929delT and 8441-15del20 deletions. Conclusions: High recurrence of the splice-site mutation 425A → G in central European patients with DEB should be taken into account when designing COL7A1 mutation detection strategies. Reporting of three novel COL7A1 mutations in this study further emphasizes the molecular heterogeneity of DEB and provides more information for studies on genotype-phenotype correlations in different DEB subtypes.

AB - Background: Mutations in the type VII collagen gene (COL7A1) are responsible for dominant and recessive forms of dystrophic epidermolysis bullosa (DEB). These mutations are usually specific for individual families; only a few cases of recurring mutations have been identified. Objectives: Forty-three unrelated Hungarian and German patients with different DEB phenotypes were screened for novel and recurrent COL7A1 mutations. Methods: All patients were classified based on clinical and genetic findings, skin immunofluorescent antigen mapping, and electron microscopic studies. Mutation analysis was performed by amplification of genomic DNA with polymerase chain reaction using COL7A1-specific primers, heteroduplex analysis, and direct nucleotide sequencing. Restriction endonuclease digestion was used for family screening and mutation verification. Results: In this group of patients, the splice-site mutation 425A → G was observed frequently, in 11 of 86 alleles (12-8%), once in homozygous form and in nine cases in heterozygous form. One of 100 control alleles from clinically unaffected individuals also carried the mutation. We also identified three novel mutations: the 976-3C → A splice-site mutation, and the 4929delT and 8441-15del20 deletions. Conclusions: High recurrence of the splice-site mutation 425A → G in central European patients with DEB should be taken into account when designing COL7A1 mutation detection strategies. Reporting of three novel COL7A1 mutations in this study further emphasizes the molecular heterogeneity of DEB and provides more information for studies on genotype-phenotype correlations in different DEB subtypes.

KW - COL7A1

KW - Dystrophic epidermolysis bullosa

KW - Genotype-phenotype

KW - Recurrent mutation

KW - Type VII collagen

UR - http://www.scopus.com/inward/record.url?scp=18944362110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18944362110&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2133.2005.06542.x

DO - 10.1111/j.1365-2133.2005.06542.x

M3 - Article

C2 - 15888141

AN - SCOPUS:18944362110

VL - 152

SP - 879

EP - 886

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 5

ER -