A recurrent frameshift mutation in exon 19 of the type VII collagen gene (COL7A1) in Mexican patients with recessive dystrophic epidermolysis bullosa

J. E. Mellerio, J. C. Salas-Alanis, M. Amaya-Guerra, E. Tamez, G. H.S. Ashton, R. Mohammedi, R. A.J. Eady, John A. McGrath

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder caused by mutations in the type VII collagen gene (COL7A1). In this study, we determined the molecular basis of autosomal recessive DEB in a 19- year-old Hispanic-Mexican woman by PCR amplification of genomic DNA, heteroduplex analysis, and automated sequencing of heteroduplex bandshifts. This approach revealed a homozygous frameshift mutation, 2470insG, in exon 19 of COL7A1 and resulted in attenuated basement membrane zone expression of type VII collagen, a reduced number of anchoring fibrils at the dermal- epidermal junction, and a sub-lamina densa level of blister formation. Clinically, the patient had widespread trauma-induced skin fragility and complete loss of the nails, but had less pseudosyndactyly of the fingers and toes and milder mucosal involvement compared to most patients with the generalized form of this genodermatosis. We also screened 7 other Hispanic- Mexican patients with recessive DEB, none of whom were known to be related to this individual, for the mutation 2470insG using heteroduplex analysis and direct sequencing and detected this mutation on 7/14 alleles. Haplotype analysis using intragenic COL7A1 and flanking polymorphisms and microsatellite markers revealed that all the mutant alleles had arisen on similar allelic backgrounds, consistent with propagation of a common Hispanic-Mexican ancestral haplotype. In view of the high allelic frequency of the mutation 2470insG in the patients studied, we recommend initial screening for this mutation when attempting to identify the molecular pathology of recessive DEB in Hispanic-Mexican patients.
Original languageEnglish
Pages (from-to)22-29
Number of pages8
JournalExperimental Dermatology
DOIs
Publication statusPublished - 1 Jan 1999
Externally publishedYes

Fingerprint

Collagen Type VII
Epidermolysis Bullosa Dystrophica
Frameshift Mutation
Exons
Skin
Hispanic Americans
Genes
Nucleic Acid Heteroduplexes
Nails
Heteroduplex Analysis
Pathology
Polymorphism
Mutation
Microsatellite Repeats
Amplification
Screening
Haplotypes
Alleles
Molecular Pathology
Toes

Cite this

Mellerio, J. E. ; Salas-Alanis, J. C. ; Amaya-Guerra, M. ; Tamez, E. ; Ashton, G. H.S. ; Mohammedi, R. ; Eady, R. A.J. ; McGrath, John A. / A recurrent frameshift mutation in exon 19 of the type VII collagen gene (COL7A1) in Mexican patients with recessive dystrophic epidermolysis bullosa. In: Experimental Dermatology. 1999 ; pp. 22-29.
@article{74061ec927774744a67c40e8d630b59e,
title = "A recurrent frameshift mutation in exon 19 of the type VII collagen gene (COL7A1) in Mexican patients with recessive dystrophic epidermolysis bullosa",
abstract = "Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder caused by mutations in the type VII collagen gene (COL7A1). In this study, we determined the molecular basis of autosomal recessive DEB in a 19- year-old Hispanic-Mexican woman by PCR amplification of genomic DNA, heteroduplex analysis, and automated sequencing of heteroduplex bandshifts. This approach revealed a homozygous frameshift mutation, 2470insG, in exon 19 of COL7A1 and resulted in attenuated basement membrane zone expression of type VII collagen, a reduced number of anchoring fibrils at the dermal- epidermal junction, and a sub-lamina densa level of blister formation. Clinically, the patient had widespread trauma-induced skin fragility and complete loss of the nails, but had less pseudosyndactyly of the fingers and toes and milder mucosal involvement compared to most patients with the generalized form of this genodermatosis. We also screened 7 other Hispanic- Mexican patients with recessive DEB, none of whom were known to be related to this individual, for the mutation 2470insG using heteroduplex analysis and direct sequencing and detected this mutation on 7/14 alleles. Haplotype analysis using intragenic COL7A1 and flanking polymorphisms and microsatellite markers revealed that all the mutant alleles had arisen on similar allelic backgrounds, consistent with propagation of a common Hispanic-Mexican ancestral haplotype. In view of the high allelic frequency of the mutation 2470insG in the patients studied, we recommend initial screening for this mutation when attempting to identify the molecular pathology of recessive DEB in Hispanic-Mexican patients.",
author = "Mellerio, {J. E.} and Salas-Alanis, {J. C.} and M. Amaya-Guerra and E. Tamez and Ashton, {G. H.S.} and R. Mohammedi and Eady, {R. A.J.} and McGrath, {John A.}",
year = "1999",
month = "1",
day = "1",
doi = "10.1111/j.1600-0625.1999.tb00344.x",
language = "English",
pages = "22--29",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell",

}

A recurrent frameshift mutation in exon 19 of the type VII collagen gene (COL7A1) in Mexican patients with recessive dystrophic epidermolysis bullosa. / Mellerio, J. E.; Salas-Alanis, J. C.; Amaya-Guerra, M.; Tamez, E.; Ashton, G. H.S.; Mohammedi, R.; Eady, R. A.J.; McGrath, John A.

In: Experimental Dermatology, 01.01.1999, p. 22-29.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A recurrent frameshift mutation in exon 19 of the type VII collagen gene (COL7A1) in Mexican patients with recessive dystrophic epidermolysis bullosa

AU - Mellerio, J. E.

AU - Salas-Alanis, J. C.

AU - Amaya-Guerra, M.

AU - Tamez, E.

AU - Ashton, G. H.S.

AU - Mohammedi, R.

AU - Eady, R. A.J.

AU - McGrath, John A.

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder caused by mutations in the type VII collagen gene (COL7A1). In this study, we determined the molecular basis of autosomal recessive DEB in a 19- year-old Hispanic-Mexican woman by PCR amplification of genomic DNA, heteroduplex analysis, and automated sequencing of heteroduplex bandshifts. This approach revealed a homozygous frameshift mutation, 2470insG, in exon 19 of COL7A1 and resulted in attenuated basement membrane zone expression of type VII collagen, a reduced number of anchoring fibrils at the dermal- epidermal junction, and a sub-lamina densa level of blister formation. Clinically, the patient had widespread trauma-induced skin fragility and complete loss of the nails, but had less pseudosyndactyly of the fingers and toes and milder mucosal involvement compared to most patients with the generalized form of this genodermatosis. We also screened 7 other Hispanic- Mexican patients with recessive DEB, none of whom were known to be related to this individual, for the mutation 2470insG using heteroduplex analysis and direct sequencing and detected this mutation on 7/14 alleles. Haplotype analysis using intragenic COL7A1 and flanking polymorphisms and microsatellite markers revealed that all the mutant alleles had arisen on similar allelic backgrounds, consistent with propagation of a common Hispanic-Mexican ancestral haplotype. In view of the high allelic frequency of the mutation 2470insG in the patients studied, we recommend initial screening for this mutation when attempting to identify the molecular pathology of recessive DEB in Hispanic-Mexican patients.

AB - Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder caused by mutations in the type VII collagen gene (COL7A1). In this study, we determined the molecular basis of autosomal recessive DEB in a 19- year-old Hispanic-Mexican woman by PCR amplification of genomic DNA, heteroduplex analysis, and automated sequencing of heteroduplex bandshifts. This approach revealed a homozygous frameshift mutation, 2470insG, in exon 19 of COL7A1 and resulted in attenuated basement membrane zone expression of type VII collagen, a reduced number of anchoring fibrils at the dermal- epidermal junction, and a sub-lamina densa level of blister formation. Clinically, the patient had widespread trauma-induced skin fragility and complete loss of the nails, but had less pseudosyndactyly of the fingers and toes and milder mucosal involvement compared to most patients with the generalized form of this genodermatosis. We also screened 7 other Hispanic- Mexican patients with recessive DEB, none of whom were known to be related to this individual, for the mutation 2470insG using heteroduplex analysis and direct sequencing and detected this mutation on 7/14 alleles. Haplotype analysis using intragenic COL7A1 and flanking polymorphisms and microsatellite markers revealed that all the mutant alleles had arisen on similar allelic backgrounds, consistent with propagation of a common Hispanic-Mexican ancestral haplotype. In view of the high allelic frequency of the mutation 2470insG in the patients studied, we recommend initial screening for this mutation when attempting to identify the molecular pathology of recessive DEB in Hispanic-Mexican patients.

U2 - 10.1111/j.1600-0625.1999.tb00344.x

DO - 10.1111/j.1600-0625.1999.tb00344.x

M3 - Article

SP - 22

EP - 29

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

ER -