Association of splicing defects in PTEN leading to exon skipping or partial intron retention in Cowden syndrome

• Published in: Human genetics Vol. 107; no. 3; pp. 234 - 238
• Main Authors: CELEBI, Julide Tok, WANNER, Molly, XIAO LI PING, HONG ZHANG, PEACOCKE, Monica
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.09.2000; Berlin; New York, NY
• Subjects: Biological and medical sciences; Child; Complex syndromes; Exons; Female; Genes, Tumor Suppressor; Germ-Line Mutation; Hamartoma Syndrome, Multiple - genetics; Humans; Introns; Male; Medical genetics; Medical sciences; Phosphoric Monoester Hydrolases - genetics; Point Mutation; PTEN Phosphohydrolase; RNA Splicing - genetics; Syndrome; Tumor Suppressor Proteins; Pseudotumor; Human; Skin disease; Splicing; Nucleotide sequence; Family study; Chromosome C10; Genetic disease; Hamartoma; Messenger RNA; Autosomal character; Benign neoplasm; Mutation; Tumor suppressor gene
• DOI: 10.1007/s004390000362
• ISSN: 0340-6717

Cowden syndrome (CS) and Bannayan Zonana syndrome (BZS) are two autosomal dominantly inherited conditions characterized by hamartomas. Mutations in PTEN, a tumor suppressor gene located on chromosome 10q23, have been identified in patients with phenotypic findings of both CS and BZS. These mutations are found throughout the entire gene, with exon 5 being the most common site, and include point mutations, insertions and deletions. To date, 11 point mutations at the splice junctions of the PTEN gene have been reported, however, data on the alterations in the transcripts have been lacking. In this study, we have identified three novel splice site mutations in PTEN, in two families with CS and in one individual with BZS. One mutation affected the splice-acceptor site, which resulted in out-of-frame skipping of an entire exon. By contrast, the other two mutations affected the splice-donor sites, and both showed inclusion of partial intronic sequences in the transcript due to activation of cryptic splice sites. These data demonstrate mRNA alterations as a consequence of splice site mutations in the PTEN gene.