Document Detail


The mutational spectrum of ENPP1 as arising after the analysis of 23 unrelated patients with generalized arterial calcification of infancy (GACI).
MedLine Citation:
PMID:  15605415     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Generalized arterial calcification of infancy (GACI), is characterized by calcification of the internal elastic lamina of large and medium-sized arteries and stenosis due to myointimal proliferation. Although survival to adulthood has been reported, most patients die within the first six months of life. Recently, we found mutations of ENPP1 coding for ecto-nucleotide pyrophosphatase/phosphodiesterase 1 to be associated with GACI in 8 of 11 families. In this study, we analyzed ENPP1 in affected individuals of another 12 unrelated families. We identified 11 novel homozygous or compound heterozygous mutations in 10 of the 12 new families. The mutations (1 nonsense, 7 missense, 1 single amino acid deletion, and 2 frame shift mutations) were scattered over the whole coding region with a slightly more condensed distribution within the catalytic and nuclease-like domain as compared to the first survey. In this study, three mutations were found repeatedly in apparently unrelated patients, 7 x c.913C>A (p.Pro305Thr) and c.2662C [corrected]>T (p.Arg888Trp) as well as c.2320C>T (p.Arg774Cys) each twice. However, haplotype analysis suggested a founder effect of British extraction for mutation c.913C>A (p.Pro305Thr). The fact that the two other mutations c.2662C [corrected]>T (p.Arg888Trp) and c.2320C>T (p.Arg774Cys) occurred twice within a single allele also suggests a single founder. This study confirms the role of ENPP1 mutations as the main cause of GACI and adds considerably to the mutational spectrum of ENPP1.
Authors:
Nico Ruf; Birgit Uhlenberg; Robert Terkeltaub; Peter Nürnberg; Frank Rutsch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Human mutation     Volume:  25     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-22     Completed Date:  2006-02-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  98     Citation Subset:  IM    
Copyright Information:
(c) 2004 Wiley-Liss, Inc.
Affiliation:
Gene Mapping Center, Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany.
Data Bank Information
Bank Name/Acc. No.:
OMIM/208000
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Arteries*
Calcinosis / genetics*
Child
DNA Mutational Analysis
Humans
Infant
Infant, Newborn
Mutation
Phosphoric Diester Hydrolases / genetics*
Pyrophosphatases / genetics*
Vascular Diseases / genetics*
Chemical
Reg. No./Substance:
EC 3.1.4.-/Phosphoric Diester Hydrolases; EC 3.1.4.1/ectonucleotide pyrophosphatase phosphodiesterase 1; EC 3.6.1.-/Pyrophosphatases
Comments/Corrections
Erratum In:
Hum Mutat. 2005 Nov;26(5):495-6

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


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