J Korean Med Sci.  2009 Apr;24(2):256-261. 10.3346/jkms.2009.24.2.256.

Type VII Collagen Gene Mutations (c.8569G>T and c.4879G>A) Result in the Moderately Severe Phenotype of Recessive Dystrophic Epidermolysis Bullosa in a Korean Patient

• Cho JW
• Nakano H
• Lee KS

• KMID: 1779127
• DOI: http://doi.org/10.3346/jkms.2009.24.2.256

Abstract

Dystrophic epidermolysis bullosa (DEB) are caused by mutations in the COL7A1 gene, which encodes type VII collagen. Even though more than 500 different COL7A1 mutations have been identified in DEB, it still remains to be under-investigated. To investigate the mutation of COL7A1 in moderately severe phenotype of recessive DEB (RDEB) in a Korean patient, the mutation detection strategy was consisted of polymerase chain reaction (PCR) amplification of genomic DNA, followed by heteroduplex analysis, nucleotide sequencing of the PCR products demonstrating altered mobility. In this study, we found that one mutation (c.8569G>T) was detected within exon 116. The mutation of c.8569G>T in exon 116 changed the GAG (Glu) to TAG, eventually resulted in premature termination of type VII collagen polypeptide. Furthermore the mother did not have the mutation c.8569G>T in exon 116. The other novel mutation (c.4879G>A) was detected within exon 51 of both patient and mother, thereby resulting in changing valine (Val) to isoleucine (Ile) in type VII collagen polypeptide. Taken together, in this study we identified compound heterozygosity for COL7A1 mutations (c.8569G>T and c.4879G>A) in moderately severe RDEB in a Korean patient. We hope that this data contribute to the expanding database on COL7A1 mutations in DEB.

Keyword

Epidermolysis Bullosa Dystrophica; COL7A1; Mutation

MeSH Terms

Adolescent
Amino Acid Substitution
Asian Continental Ancestry Group/*genetics
Collagen Type VII/*genetics
DNA Mutational Analysis
Epidermolysis Bullosa Dystrophica/*genetics/pathology
Heterozygote
Humans
Korea
Male
Pedigree
Phenotype
Point Mutation
Polymerase Chain Reaction

Figure

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  Fig. 1 Clinical features. Blisters and erosions were seen on the trunk (A, B) as well as milia (inset). Acral scaring and loss of finger and toe nail (C, D).

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  Fig. 2 The schematic presentation of the pedigree of the patient. The black arrow indicates the patient.

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  Fig. 3 Histological findings. Subepidermal blister formation and flattened rete ridges are observed (A) (H&E, ×200). Electron micrograph showing a few amount of anchoring fibrils (arrow heads) beneath the lamina densa (LD) (B).

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  Fig. 4 Identification of the mutations in COL7A1 in patient. Direct sequencing of the patient PCR product revealed G to T transition at position 8569 (A). As a result, the codon for Glu (GAG) is changed to a codon for stop (TAG). This mutation was confirmed by restriction enzyme, XspI (C). Schematic representation of the domain structure of procollagen VII and the location of the premature stop codon (E2857X) in exon 116 (D). Cysteine residues are marked as a "C", and an asterisk (*) shows the procollagen C-proteinase cleavage site.

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  Fig. 5 Identification of the mutations in COL7A1 in the patient and mother. Direct sequencing of the patient PCR product revealed G to A transition at position 4879 (A). As a result, the codon for Val (GUU) is changed to a codon for Ile (AUU). This mutation was confirmed by restriction enzyme, Alw NI (B).

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