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rdf:type |
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lifeskim:mentions |
umls-concept:C0011900,
umls-concept:C0017428,
umls-concept:C0019904,
umls-concept:C0030705,
umls-concept:C0336791,
umls-concept:C0439831,
umls-concept:C0443131,
umls-concept:C1283195,
umls-concept:C1527178,
umls-concept:C1705938,
umls-concept:C1869123
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pubmed:issue |
3
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pubmed:dateCreated |
2011-5-3
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pubmed:databankReference |
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pubmed:abstractText |
A large number of novel disease genes have been identified by homozygosity mapping and the positional candidate approach. In this study we used single nucleotide polymorphism (SNP) array-based, whole genome homozygosity mapping as the first step to a molecular diagnosis in the highly heterogeneous muscle disease, limb girdle muscular dystrophy (LGMD). In a consanguineous family, both affected siblings showed homozygous blocks on chromosome 15 corresponding to the LGMD2A locus. Direct sequencing of CAPN3, encoding calpain-3, identified a homozygous deletion c.483delG (p.Ile162SerfsX17). In a sporadic LGMD patient complete absence of caveolin-3 on Western blot was observed. However, a mutation in CAV3 could not be detected. Homozygosity mapping revealed a large homozygous block at the LGMD2I locus, and direct sequencing of FKRP encoding fukutin-related-protein detected the common homozygous c.826 C>A (p.Leu276Ile) mutation. Subsequent re-examination of this patient's muscle biopsy showed aberrant ?-dystroglycan glycosylation. In summary, we show that whole-genome homozygosity mapping using low cost SNP arrays provides a fast and non-invasive method to identify disease-causing mutations in sporadic patients or sibs from consanguineous families in LGMD2. Furthermore, this is the first study describing that in addition to PTRF, encoding polymerase I and transcript release factor, FKRP mutations may cause secondary caveolin-3 deficiency.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-15060126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-15580566,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-15726252,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-16650086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-17260395,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-18028188,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-18760389,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-18769252,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-19165332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-19465395,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-19726876,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-19842213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-5432063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21172462-9190890
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
1878-0849
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pubmed:author |
pubmed-author:Auer-GrumbachMichaelaM,
pubmed-author:BittnerReginald ERE,
pubmed-author:FischerCarinaC,
pubmed-author:FischerDirkD,
pubmed-author:GruberKarinK,
pubmed-author:HöftbergerRomanaR,
pubmed-author:JaneckeAndreas RAR,
pubmed-author:Papi?LeaL,
pubmed-author:PieberThomas RTR,
pubmed-author:SchabhüttlMariaM,
pubmed-author:SchmidtWolfgang MWM,
pubmed-author:StröbelThomasT,
pubmed-author:TrajanoskiSlaveS
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
54
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
214-9
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pubmed:meshHeading |
pubmed-meshheading:21172462-Adolescent,
pubmed-meshheading:21172462-Adult,
pubmed-meshheading:21172462-Base Sequence,
pubmed-meshheading:21172462-Blotting, Western,
pubmed-meshheading:21172462-Calpain,
pubmed-meshheading:21172462-Caveolin 3,
pubmed-meshheading:21172462-Child,
pubmed-meshheading:21172462-Chromosome Mapping,
pubmed-meshheading:21172462-Consanguinity,
pubmed-meshheading:21172462-DNA Mutational Analysis,
pubmed-meshheading:21172462-Family Health,
pubmed-meshheading:21172462-Female,
pubmed-meshheading:21172462-Genome, Human,
pubmed-meshheading:21172462-Genome-Wide Association Study,
pubmed-meshheading:21172462-Genotype,
pubmed-meshheading:21172462-Homozygote,
pubmed-meshheading:21172462-Humans,
pubmed-meshheading:21172462-Male,
pubmed-meshheading:21172462-Muscle Proteins,
pubmed-meshheading:21172462-Muscular Dystrophies, Limb-Girdle,
pubmed-meshheading:21172462-Mutation,
pubmed-meshheading:21172462-Pedigree,
pubmed-meshheading:21172462-Polymorphism, Single Nucleotide,
pubmed-meshheading:21172462-Proteins
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pubmed:articleTitle |
SNP-array based whole genome homozygosity mapping: a quick and powerful tool to achieve an accurate diagnosis in LGMD2 patients.
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pubmed:affiliation |
Department of Internal Medicine, Division of Diabetes and Metabolism, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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