PMID- 12210318
OWN - NLM
STAT- MEDLINE
DCOM- 20030212
LR  - 20161124
IS  - 0148-7299 (Print)
IS  - 0148-7299 (Linking)
VI  - 111
IP  - 3
DP  - 2002 Aug 15
TI  - Familial interstitial 570 kbp deletion of the UBE3A gene region causing Angelman 
      syndrome but not Prader-Willi syndrome.
PG  - 233-7
AB  - Angelman syndrome (AS) is a disorder of psychomotor development caused by loss of 
      function of the imprinted UBE3A gene. Since the paternal UBE3A copy is regularly 
      silent, only mutations inactivating the maternal copy cause AS. Among 1,272 
      patients suspected of AS, we found one with an isolated deletion of the UBE3A 
      gene on the maternally inherited chromosome. Initial DNA methylation testing at 
      the SNURF-SNRPN locus in the patient revealed a normal pattern. The deletion was 
      only detected through allelic loss at microsatellite loci D15S1506, D15S122, and 
      D15S210, and confirmed with fluorescence in situ hybridization (FISH) using 
      bacterial artificial chromosome (BAC) probes derived from the loci. It extends 
      approximately 570 kilobase pairs (kbp), encompassing the UBE3A locus, and is 
      flanked by loci PAR/SN and D15S986. The deletion is familial, and haplotype 
      studies suggest that a great grandfather of the index patient already carried 
      this deletion, and that it causes AS when inherited through the female germline 
      but not Prader-Willi syndrome (PWS) when paternally inherited. Our findings 
      support the hypothesis that the functional loss of maternal UBE3A gene activity 
      is sufficient to cause AS and that the deleted region does not contain genes or 
      other structures that are involved in PWS. Finally, this case highlights that 
      methylation tests can fail to detect some familial AS cases with a recurrence 
      risk of 50%.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Burger, Joachim
AU  - Burger J
AD  - Institute of Human Genetics, Charite, Humboldt-Universitat, Berlin, Germany.
FAU - Horn, Denise
AU  - Horn D
FAU - Tonnies, Holger
AU  - Tonnies H
FAU - Neitzel, Heidemarie
AU  - Neitzel H
FAU - Reis, Andre
AU  - Reis A
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Med Genet
JT  - American journal of medical genetics
JID - 7708900
RN  - EC 2.3.2.26 (UBE3A protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Angelman Syndrome/etiology/*genetics
MH  - Base Sequence
MH  - Child, Preschool
MH  - Chromosomes, Human, Pair 15
MH  - DNA Methylation
MH  - Female
MH  - Haplotypes
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Ligases/*genetics
MH  - Male
MH  - Microsatellite Repeats
MH  - Pedigree
MH  - Prader-Willi Syndrome/etiology/*genetics
MH  - *Sequence Deletion
MH  - Ubiquitin-Protein Ligases
EDAT- 2002/09/05 10:00
MHDA- 2003/02/14 04:00
CRDT- 2002/09/05 10:00
PHST- 2002/09/05 10:00 [pubmed]
PHST- 2003/02/14 04:00 [medline]
PHST- 2002/09/05 10:00 [entrez]
AID - 10.1002/ajmg.10498 [doi]
PST - ppublish
SO  - Am J Med Genet. 2002 Aug 15;111(3):233-7. doi: 10.1002/ajmg.10498.