title: PTEN c.511C>T nonsense mutation in a BRRS family disrupts a potential exonic splicing enhancer and causes exon skipping.
abstract: Bannayan-Riley-Ruvalcaba syndrome (BRRS) is an autosomal dominant disorder characterized by macrocephaly, intestinal hamartomatous polyps, lipomas and pigmented macules of the glans penis. We identified a Thai family affected with BRRS. In addition to typical manifestations of BRRS, the proband has a large hepatic AVM which is rarely found in BRRS. The molecular analysis revealed affected members were heterozygous for an exon skipping-associated nonsense mutation c.511C>T in the PTEN gene. The mutation was previously assumed to be deleterious by causing a change to a termination codon, Q171X. We, herein, found that another pathogenic effect was splicing related by disrupting a potential exonic splicing enhancer (ESE) and causing an entire exon 6 skipping. The results prompted us to investigate other reported missense/nonsense mutations in the PTEN gene. We found that they do not colocalize with ESE sites, suggesting that most of their pathogenic effects are not through ESE disruption.
authors.affiliation: Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Kanya
authors.initials: K
authors.lastname: Suphapeetiporn
authors.forename: Pradermchai
authors.initials: P
authors.lastname: Kongkam
authors.forename: Jarturon
authors.initials: J
authors.lastname: Tantivatana
authors.forename: Thivaratana
authors.initials: T
authors.lastname: Sinthuwiwat
authors.forename: Siraprapa
authors.initials: S
authors.lastname: Tongkobpetch
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
mesh_terms: D005091:Exons / Q000235:genetics*; D005260:Female; D006223:Hamartoma Syndrome, Multiple / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*
chemical_list: D038621:Regulatory Sequences, Ribonucleic Acid; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human