Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa

Jemima E. Mellerio, Gabrielle H.S. Ashton, Rafik Mohammedi, Calum C. Lyon, Brian Kirby, Karen E. Harman, Julio C. Salas-Alanis, David J. Atherton, Phillip V. Harrison, W. Andrew D. Griffiths, Martin M. Black, Robin A.J. Eady, John A. McGrath

Research output: Contribution to journalArticle

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Abstract

The inherited mechanobullous disease, dystrophic epidermolysis bullosa, is caused by type VII collagen gene (COL7A1) mutations. We studied six unrelated patients with a distinct clinical subtype of this disease, epidermolysis bullosa pruriginosa, characterized by pruritus, excoriated prurigo nodules, and skin fragility. Mutation analysis using polymerase chain reaction amplification of genomic DNA, heteroduplex analysis and direct nucleotide sequencing demonstrated pathogenetic COL7A1 mutations in each case. Four patients had a glycine substitution mutation on one COL7A1 allele (G1791E, G2242R, G2369S, and G2713R), a fifth was a compound heterozygote for a splice site mutation (5532 + 1G-to-A) and a single base pair deletion (7786delG), and a sixth patient was heterozygous for an out-of-frame deletion mutation (6863del16). This study shows that the molecular pathology in patients with the distinctive clinical features of epidermolysis bullosa pruriginosa is heterogeneous and suggests that other factors, in addition to the inherent COL7A1 mutation(s), may be responsible for an epidermolysis bullosa pruriginosa phenotype.
Original languageEnglish
Pages (from-to)984-987
Number of pages4
JournalJournal of Investigative Dermatology
DOIs
Publication statusPublished - 1 Jan 1999
Externally publishedYes

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Collagen Type VII
Nucleic Acid Heteroduplexes
Mutation
Polymerase chain reaction
Pathology
Glycine
Amplification
Skin
Frameshift Mutation
Substitution reactions
Nucleotides
Genes
Heteroduplex Analysis
Prurigo
Epidermolysis Bullosa Dystrophica
Molecular Pathology
Sequence Deletion
Pruritus
Heterozygote
Base Pairing

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Mellerio, J. E., Ashton, G. H. S., Mohammedi, R., Lyon, C. C., Kirby, B., Harman, K. E., ... McGrath, J. A. (1999). Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa. Journal of Investigative Dermatology, 984-987. https://doi.org/10.1046/j.1523-1747.1999.00614.x
Mellerio, Jemima E. ; Ashton, Gabrielle H.S. ; Mohammedi, Rafik ; Lyon, Calum C. ; Kirby, Brian ; Harman, Karen E. ; Salas-Alanis, Julio C. ; Atherton, David J. ; Harrison, Phillip V. ; Griffiths, W. Andrew D. ; Black, Martin M. ; Eady, Robin A.J. ; McGrath, John A. / Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa. In: Journal of Investigative Dermatology. 1999 ; pp. 984-987.
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abstract = "The inherited mechanobullous disease, dystrophic epidermolysis bullosa, is caused by type VII collagen gene (COL7A1) mutations. We studied six unrelated patients with a distinct clinical subtype of this disease, epidermolysis bullosa pruriginosa, characterized by pruritus, excoriated prurigo nodules, and skin fragility. Mutation analysis using polymerase chain reaction amplification of genomic DNA, heteroduplex analysis and direct nucleotide sequencing demonstrated pathogenetic COL7A1 mutations in each case. Four patients had a glycine substitution mutation on one COL7A1 allele (G1791E, G2242R, G2369S, and G2713R), a fifth was a compound heterozygote for a splice site mutation (5532 + 1G-to-A) and a single base pair deletion (7786delG), and a sixth patient was heterozygous for an out-of-frame deletion mutation (6863del16). This study shows that the molecular pathology in patients with the distinctive clinical features of epidermolysis bullosa pruriginosa is heterogeneous and suggests that other factors, in addition to the inherent COL7A1 mutation(s), may be responsible for an epidermolysis bullosa pruriginosa phenotype.",
author = "Mellerio, {Jemima E.} and Ashton, {Gabrielle H.S.} and Rafik Mohammedi and Lyon, {Calum C.} and Brian Kirby and Harman, {Karen E.} and Salas-Alanis, {Julio C.} and Atherton, {David J.} and Harrison, {Phillip V.} and Griffiths, {W. Andrew D.} and Black, {Martin M.} and Eady, {Robin A.J.} and McGrath, {John A.}",
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Mellerio, JE, Ashton, GHS, Mohammedi, R, Lyon, CC, Kirby, B, Harman, KE, Salas-Alanis, JC, Atherton, DJ, Harrison, PV, Griffiths, WAD, Black, MM, Eady, RAJ & McGrath, JA 1999, 'Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa', Journal of Investigative Dermatology, pp. 984-987. https://doi.org/10.1046/j.1523-1747.1999.00614.x

Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa. / Mellerio, Jemima E.; Ashton, Gabrielle H.S.; Mohammedi, Rafik; Lyon, Calum C.; Kirby, Brian; Harman, Karen E.; Salas-Alanis, Julio C.; Atherton, David J.; Harrison, Phillip V.; Griffiths, W. Andrew D.; Black, Martin M.; Eady, Robin A.J.; McGrath, John A.

In: Journal of Investigative Dermatology, 01.01.1999, p. 984-987.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa

AU - Mellerio, Jemima E.

AU - Ashton, Gabrielle H.S.

AU - Mohammedi, Rafik

AU - Lyon, Calum C.

AU - Kirby, Brian

AU - Harman, Karen E.

AU - Salas-Alanis, Julio C.

AU - Atherton, David J.

AU - Harrison, Phillip V.

AU - Griffiths, W. Andrew D.

AU - Black, Martin M.

AU - Eady, Robin A.J.

AU - McGrath, John A.

PY - 1999/1/1

Y1 - 1999/1/1

N2 - The inherited mechanobullous disease, dystrophic epidermolysis bullosa, is caused by type VII collagen gene (COL7A1) mutations. We studied six unrelated patients with a distinct clinical subtype of this disease, epidermolysis bullosa pruriginosa, characterized by pruritus, excoriated prurigo nodules, and skin fragility. Mutation analysis using polymerase chain reaction amplification of genomic DNA, heteroduplex analysis and direct nucleotide sequencing demonstrated pathogenetic COL7A1 mutations in each case. Four patients had a glycine substitution mutation on one COL7A1 allele (G1791E, G2242R, G2369S, and G2713R), a fifth was a compound heterozygote for a splice site mutation (5532 + 1G-to-A) and a single base pair deletion (7786delG), and a sixth patient was heterozygous for an out-of-frame deletion mutation (6863del16). This study shows that the molecular pathology in patients with the distinctive clinical features of epidermolysis bullosa pruriginosa is heterogeneous and suggests that other factors, in addition to the inherent COL7A1 mutation(s), may be responsible for an epidermolysis bullosa pruriginosa phenotype.

AB - The inherited mechanobullous disease, dystrophic epidermolysis bullosa, is caused by type VII collagen gene (COL7A1) mutations. We studied six unrelated patients with a distinct clinical subtype of this disease, epidermolysis bullosa pruriginosa, characterized by pruritus, excoriated prurigo nodules, and skin fragility. Mutation analysis using polymerase chain reaction amplification of genomic DNA, heteroduplex analysis and direct nucleotide sequencing demonstrated pathogenetic COL7A1 mutations in each case. Four patients had a glycine substitution mutation on one COL7A1 allele (G1791E, G2242R, G2369S, and G2713R), a fifth was a compound heterozygote for a splice site mutation (5532 + 1G-to-A) and a single base pair deletion (7786delG), and a sixth patient was heterozygous for an out-of-frame deletion mutation (6863del16). This study shows that the molecular pathology in patients with the distinctive clinical features of epidermolysis bullosa pruriginosa is heterogeneous and suggests that other factors, in addition to the inherent COL7A1 mutation(s), may be responsible for an epidermolysis bullosa pruriginosa phenotype.

U2 - 10.1046/j.1523-1747.1999.00614.x

DO - 10.1046/j.1523-1747.1999.00614.x

M3 - Article

SP - 984

EP - 987

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

ER -