{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:16:33Z","timestamp":1760782593009},"reference-count":10,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,4,13]],"date-time":"2004-04-13T00:00:00Z","timestamp":1081814400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited skin disease caused by mutations in the gene encoding type VII collagen (COL7A1). The mutations are highly variable and this greatly complicates the study of the genotype\u2013phenotype relationships. To date, three recurrent mutations, specific to Japanese RDEB patients have been reported. By comparing the phenotypes of RDEB patients with different recurrent mutations, the upstream positions of the premature termination codons (PTCs) showed strong correlation with the RDEB clinical disease severity. However, such correlations have not been supported by patients with mutations that were different from these recurrent Japanese patients mutations. In this study, we report a case of RDEB with a very mild clinical phenotype, who was a compound heterozygote harbouring both a recurrent Japanese mutation and a novel deletion mutation resulting in a more upstream PTC. The patient and his mother were shown to have a recurrent donor splice site mutation within intron 81 (6573\u2003+\u20031G\u2003&gt;\u2003C), a recurrent Japanese mutation that activates a cryptic donor splicing site and results in a downstream PTC. The patient and his father shared a single\u2010nucleotide deletion within exon 64 (5504delA), which causes a downstream frame shift in five amino acids before creating a PTC. Occurrence of the PTCs in mRNA was confirmed by reverse transcription\u2010polymerase chain reaction (RT)\u2010PCR. The patient's skin showed reduced immunofluorescence staining for COL7A1 and reduced number of abnormal or short anchoring fibrils by electron microscopy. Although the position of the mutation 5504delA PTC was located upstream of the previous mutations reported in combination with the 6573\u2003+\u20031G\u2003&gt;\u2003C mutation, the two mutations together give an apparently milder clinical phenotype. Therefore, genotype\u2013phenotype relationships in RDEB cannot be explained purely by the position of PTC.<\/jats:p>","DOI":"10.1111\/j.0906-6705.2004.00167.x","type":"journal-article","created":{"date-parts":[[2004,4,13]],"date-time":"2004-04-13T15:51:34Z","timestamp":1081871494000},"page":"229-233","source":"Crossref","is-referenced-by-count":12,"title":["Does the position of the premature termination codon in COL7A1 correlate with the clinical severity in recessive dystrophic epidermolysis bullosa?"],"prefix":"10.1111","volume":"13","author":[{"given":"Akira","family":"Ishiko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuji","family":"Masunaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Ota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeji","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,4,13]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(91)70021-S"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.1996.tb00086.x"},{"key":"e_1_2_6_4_2","first-page":"671","article-title":"Glycine substitutions in the triple\u2010helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance","volume":"58","author":"Christiano A M","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.4.1577"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1238"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12471830"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1999.00601.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12329600"},{"key":"e_1_2_6_10_2","first-page":"209","article-title":"Compound heterozygosity for a nonsense mutation and a splice site mutation in the type VII collagen gene (COL7A1) in recessive dystrophic epidermolysis bullosa","volume":"76","author":"Tamai K","year":"1997","journal-title":"Lab Invest"},{"key":"e_1_2_6_11_2","first-page":"1483","article-title":"Restoration of open reading frame resulting from skipping of an exon with an internal deletion in the COL7A1 gene","volume":"78","author":"Cserhalmi\u2010Friedman P B","year":"1998","journal-title":"Lab Invest"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.0906-6705.2004.00167.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.0906-6705.2004.00167.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T20:26:31Z","timestamp":1696969591000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.0906-6705.2004.00167.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4]]},"references-count":10,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1111\/j.0906-6705.2004.00167.x"],"URL":"https:\/\/doi.org\/10.1111\/j.0906-6705.2004.00167.x","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,4]]}}}