Document Detail

Molecular mechanism of angelman syndrome in two large families involves an imprinting mutation.
MedLine Citation:
PMID:  9973277     Owner:  NLM     Status:  MEDLINE    
Patients with Angelman syndrome (AS) and Prader-Willi syndrome with mutations in the imprinting process have biparental inheritance but uniparental DNA methylation and gene expression throughout band 15q11-q13. In several of these patients, microdeletions upstream of the SNRPN gene have been identified, defining an imprinting center (IC) that has been hypothesized to control the imprint switch process in the female and male germlines. We have now identified two large families (AS-O and AS-F) segregating an AS imprinting mutation, including one family originally described in the first genetic linkage of AS to 15q11-q13. This demonstrates that this original linkage is for the 15q11-q13 IC. Affected patients in the AS families have either a 5.5- or a 15-kb microdeletion, one of which narrowed the shortest region of deletion overlap to 1.15 kb in all eight cases. This small region defines a component of the IC involved in AS (ie., the paternal-to-maternal switch element). The presence of an inherited imprinting mutation in multiple unaffected members of these two families, who are at risk for transmitting the mutation to affected children or children of their daughters, raises important genetic counseling issues.
T Ohta; K Buiting; H Kokkonen; S McCandless; S Heeger; H Leisti; D J Driscoll; S B Cassidy; B Horsthemke; R D Nicholls
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of human genetics     Volume:  64     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-04-13     Completed Date:  1999-04-13     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  385-96     Citation Subset:  IM    
Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4955, USA.
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MeSH Terms
Angelman Syndrome / genetics*
DNA Methylation
Genomic Imprinting*
Polymerase Chain Reaction
Sequence Deletion

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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