title: Novel UBE3A mutations causing Angelman syndrome: different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions.
abstract: Angelman syndrome (AS) is a genetic disorder caused by a deficiency of UBE3A imprinted gene expression from the maternal chromosome 15. In 10% of AS cases the genetic cause is a mutation affecting the maternal copy of the UBE3A gene. In two large Spanish series of clinically stringently selected and nonstringently selected patients, we have identified 11 pathological mutations--eight of them novel mutations--and 14 sequence changes considered polymorphic variants. Remarkably, single nucleotide substitutions are more likely to be inherited, while multiple nucleotide deletions or insertions are less frequently inherited, thus indicating that single nucleotide substitutions are more likely to originate from the paternal germline. Additionally, there seems to be a different distribution of nucleotide changes and multiple nucleotide deletions or insertions along the UBE3A gene sequence.
authors.affiliation: Unitat de Biologia Cel.lular, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. cristina.camprubi@uab.es
authors.forename: Cristina
authors.initials: C
authors.lastname: Camprubí
authors.forename: Miriam
authors.initials: M
authors.lastname: Guitart
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Gabau
authors.forename: Maria Dolors
authors.initials: MD
authors.lastname: Coll
authors.forename: Sergi
authors.initials: S
authors.lastname: Villatoro
authors.forename: Silvestre
authors.initials: S
authors.lastname: Oltra
authors.forename: Monica
authors.initials: M
authors.lastname: Roselló
authors.forename: Irene
authors.initials: I
authors.lastname: Ferrer
authors.forename: Sandra
authors.initials: S
authors.lastname: Monfort
authors.forename: Carmen
authors.initials: C
authors.lastname: Orellana
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez
mesh_terms: D000595:Amino Acid Sequence; D017204:Angelman Syndrome / Q000235:genetics*; D001483:Base Sequence; D003062:Codon; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005220:Fathers; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D035781:Siblings; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D003062:Codon; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases