Novel UBE3A mutations causing Angelman syndrome: different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions.
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.
Camprubí
Cristina
C
Unitat de Biologia Cel.lular, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. cristina.camprubi@uab.es
Guitart
Miriam
M
Gabau
Elisabeth
E
Coll
Maria Dolors
MD
Villatoro
Sergi
S
Oltra
Silvestre
S
Roselló
Monica
M
Ferrer
Irene
I
Monfort
Sandra
S
Orellana
Carmen
C
Martínez
Francisco
F
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*
D003062:Codon; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases