Splice site mutation in COL7A1 resulting in aberrant in‐frame transcripts identified in a case of recessive dystrophic epidermolysis bullosa, pretibial

Abstract

Dystrophic epidermolysis bullosa (DEB), pretibial, a rare subtype of epidermolysis bullosa (EB), is characterized by recurrent blisters and erosions predominantly on the pretibial region. We report the case of a 60-year-old Japanese woman with persistent blistering eruptions and scar formation on the pretibial region and elbows. Mutational analysis revealed a previously reported c.5797C>T mutation in exon 70 (p.R1933X) and a novel c.6348+1G>A mutation in intron 76 of COL7A1. Reverse transcription polymerase chain reaction revealed that the c.6348+1G>A mutation resulted in the skipping of exon 76 (69 bp) and the retention of intron 76 (75 bp), and both transcripts were in-frame. From these results, we diagnosed the patient as having recessive DEB, pretibial. A review of previously reported mutations in DEB, pretibial, revealed that one-third of DEB, pretibial, cases showed a recessive inheritance pattern, and no case had a combination of premature termination codon (PTC)/PTC mutations. The DEB, pretibial, case described herein is the first reported case of a compound heterozygote with PTC/in-frame mutations. Although no special characteristic features of the mutations were identified, a high diversity of COL7A1 mutations was shown even in DEB, pretibial.

Morphological and morphometric analysis of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa: a retrospective study

“…1 This form is caused by premature stop codons in the COL7A1 gene transcript, that yields smaller than normal collagen VII proteins that are unable to guarantee anchorage between epidermis and dermis. [2][3][4] Among the disease complications, there is an increased risk of an aggressive form of cutaneous squamous cell carcinoma (cSCC). The mean age at diagnosis of this tumour in epidermolysis bullosa patients is approximately 36 years (range 27-48 years), whereas it is generally diagnosed at about 80 years (range 73-86 years) 5 in non-epidermolysis bullosa subjects.…”

Pretibial dystrophic epidermolysis bullosa associated with aberrant exon splicing of type VII collagen

“… 5 Two patients with splice site mutations prior to our patient have been reported. 5 , 6 We provide a previously unreported dominant mutation associated with exon skipping, supporting genomic investigations for similar dermatologic cases presenting during adulthood.…”

“…Familial cases of dominant inheritance in Taiwan, Japan, China, Finland, and Belgium have been studied, with pedigrees displaying glycine substitution mutations in the C-terminal portion of COL7A1 . 3 , 4 , 5 Recessive cases have been reported at about half the rate of dominant cases, with mutations alternatively distributed along the entire length of the COL7A1 gene. 5 Two patients with splice site mutations prior to our patient have been reported.…”

“…3 , 4 , 5 Recessive cases have been reported at about half the rate of dominant cases, with mutations alternatively distributed along the entire length of the COL7A1 gene. 5 Two patients with splice site mutations prior to our patient have been reported. 5 , 6 We provide a previously unreported dominant mutation associated with exon skipping, supporting genomic investigations for similar dermatologic cases presenting during adulthood.…”

Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa

“…=NANANAheterogeneous exon 74 skipDDEB-gennormaldthis paper (EB-072)9c.6215del (p.Gly2061_Gln2072del)7474dominantc. =NANANAheterogeneous exon 74 skipDDEB-prnormal 16 10c.6348+1G>A (p.Val2094_Lys2116del)IVS7676recessivec.5797C>T (p.Arg1933*)NANArecessivehomogeneous exon 76 skipRDEB-prnormal 49 11c.6832-23_6832-3del (p.Gly2278_Gln2300del)IVS8687dominantc. =NANANAheterogeneous exon 87 skipDDEB-acnormaldthis paper (EB-156)12c.6846G>C (p.Gly2278_Gln2300del)8787dominantc.…”