Novel UBE3A mutations causing Angelman syndrome: different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions.

Autores de IIS La Fe

• Maria Dolors Coll Sandiumenge

  Autor

• Juan Silvestre Oltra Soler

  Autor

• Mónica Pilar Roselló Piera

  Autor

• Isabel Ferrer Bradley

  Autor

• Sandra Monfort Membrado

  Autor

• Carmen Orellana Alonso

  Autor

• 

  Francisco Martínez Castellano

  Autor

Participantes ajenos a IIS La Fe

• Camprubí C
• Guitart M
• Gabau E
• Villatoro S

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.