Abstract:
BACKGROUND:Junctional epidermolysis bullosa (JEB), a group of hereditary skin fragility disorders, is associated with a wide variety of phenotypes, although all forms are characterised by trauma induced skin blistering and tissue separation at the dermal-epidermal junction zone. A subgroup, coined JEB-other, is associated with mutations in the COL17A1 gene encoding collagen XVII or, more rarely, with mutations in the laminin 332 genes LAMA3, LAMB3, or LAMC2. The objective of this study is comprehensive genotype-phenotype analysis in JEB-other patients with COL17A1 mutations and elucidation of disease mechanisms underlying different skin phenotypes. METHODS AND RESULTS:COL17A1 mutations and their clinical and cellular consequences were systematically analysed in 43 patients with JEB-other. Cell culture, RT-PCR, and protein biochemistry were applied to assess the effects of splice site mutations-that is, the nature and amounts of transcripts and polypeptides synthesised and their association with the phenotypic outcome. 34 distinct COL17A1 mutations were disclosed, 12 of them novel. mRNA and protein analyses demonstrated that patients with only about 12-14% of the physiological collagen XVII levels had mild cutaneous involvement and a long life span. CONCLUSIONS:In contrast to complete null phenotypes, presence of minor amounts of collagen XVII protein in JEB skin is associated with mild phenotypic manifestations. The data have significant implications for design of molecular therapies for JEB, since they suggest that already a low extent of collagen XVII restoration will improve skin stability and alleviate symptoms.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Kiritsi D,Kern JS,Schumann H,Kohlhase J,Has C,Bruckner-Tuderman Ldoi
10.1136/jmg.2010.086751subject
Has Abstractpub_date
2011-07-01 00:00:00pages
450-7issue
7eissn
0022-2593issn
1468-6244pii
jmg.2010.086751journal_volume
48pub_type
杂志文章abstract:BACKGROUND:Results of a Scandinavian genome scan in type 1 diabetes mellitus (T1D) have recently been reported. Among the novel, not previously reported chromosomal regions showing linkage to T1D was a region on chromosome 21. OBJECTIVE:To fine map this region on chromosome 21. METHODS AND RESULTS:The linked region w...
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更新日期:1989-08-01 00:00:00