Details

Autor(en) / Beteiligte

• Spier, Isabel
• Horpaopan, Sukanya
• Vogt, Stefanie
• Uhlhaas, Siegfried
• Morak, Monika
• Stienen, Dietlinde
• Draaken, Markus
• Ludwig, Michael
• Holinski-Feder, Elke
• Nöthen, Markus M.
• Hoffmann, Per
• Aretz, Stefan

Titel

Deep intronic APC mutations explain a substantial proportion of patients with familial or early-onset adenomatous polyposis

Ist Teil von

• Human mutation, 2012-07, Vol.33 (7), p.1045-1050

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Wiley Online Library

Beschreibungen/Notizen

• To uncover pathogenic deep intronic variants in patients with colorectal adenomatous polyposis, in whom no germline mutation in the APC or MUTYH genes can be identified by routine diagnostics, we performed a systematic APC messenger RNA analysis in 125 unrelated mutation‐negative cases. Overall, we identified aberrant transcripts in 8% of the patients (familial cases 30%; early‐onset manifestation 21%). In eight of them, two different out‐of‐frame pseudoexons were found consisting of a 167‐bp insertion from intron 4 in five families with a shared founder haplotype and a 83‐bp insertion from intron 10 in three patients. The pseudoexon formation was caused by three different heterozygous germline mutations, which are supposed to activate cryptic splice sites. In conclusion, a few deep intronic mutations contribute substantially to the APC mutation spectrum. Complementary DNA analysis and/or target sequencing of intronic regions should be considered as an additional mutation discovery approach in polyposis patients. Hum Mutat 33:1045–1050, 2012. © 2012 Wiley Periodicals, Inc.