| Autor: |
Aicha Salhi, Rudolf Happle, Julie V. Schaffer, Silvestre Oltra, Arne König, Bregje W.M. van Bon, Francisco Martínez, Dorothea Bornholdt, Frank Oeffner, Karl-Heinz Grzeschik, Ulrike Neidel, Sandra Monfort |
| Rok vydání: |
2011 |
| Předmět: |
|
| Zdroj: |
Experimental Dermatology. 20:447-449 |
| ISSN: |
0906-6705 |
| DOI: |
10.1111/j.1600-0625.2010.01238.x |
| Popis: |
Ichthyosis follicularis, alopecia and photophobia (IFAP) syndrome is an X-linked genodermatosis with congenital atrichia being the most prominent feature. Recently, we have shown that functional deficiency of MBTPS2 (membrane-bound transcription factor protease site 2) - a zinc metalloprotease essential for cholesterol homeostasis and endoplasmic reticulum stress response - causes the disease. Here, we present results obtained by analysing two intronic MBTPS2 mutations, c.671-9T>G and c.225-6T>A, using in silico and cell-based splicing assays. Accordingly, the c.225-6T>A transversion generated a new splice acceptor site, which caused extension of exon 3 by four bases and subsequently introduced a premature stop codon. Both, minigene experiments and RT-PCR analysis with patient-derived mRNA, demonstrated that the c.671-9T>G mutation resulted in skipping of exon 6, most likely because of disruption of the polypyrimidin tract or a putative intronic splicing enhancer (ISE). Our combined biocomputational and experimental analysis strongly suggested that both intronic alterations are disease-causing mutations. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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