Linked Life Data

1513469

Source:http://linkedlifedata.com/resource/pubmed/id/1513469

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1992-10-1
pubmed:abstractText
We identified a premature chain termination mutation in two brothers with Duchenne muscular dystrophy and correlated the mutation in one of the brothers with immunologic detection of dystrophin in skeletal muscle. Southern and polymerase chain reaction (PCR) studies of genomic DNA from the affected boys showed no major gene rearrangements. However, the noted absence of a HindIII Southern fragment containing the proximal portion of exon 48 led to the identification of a point mutation that creates a new HindIII restriction site in that exon. Exon 48 was amplified by PCR from DNA of the patients and other family members and digested with HindIII to show the mutation in the two boys and also in their mother and maternal grandmother. Direct DNA sequencing demonstrated a cytosine-to-thymine transition at nucleotide 7163 of dystrophin that converts a glutamine codon (CAA) to an ochre chain termination codon (UAA). This mutation predicts a truncated dystrophin missing the distal spectrin-like repeat region, the cysteine-rich domain, and the carboxy terminal. Immunohistochemistry of skeletal muscle from one of the affected boys revealed membrane-localized dystrophin in the majority of fibers detected by anti-dystrophin antibodies against (1) the amino terminal and (2) part of the spectrin-like repeat region; both regions would be present in the truncated dystrophin predicted by the chain termination mutation. This suggests that the carboxy terminal may not be an absolute requirement for dystrophin membrane localization. Very few muscle fibers also showed peripheral immunostaining using anti-dystrophin antibodies against the carboxy terminal, suggesting gene reversion, suppression, or read-through in these rare fibers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0028-3878
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1775-82
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Premature chain termination mutation causing Duchenne muscular dystrophy.
pubmed:affiliation
Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX 77030.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Case Reports, Research Support, Non-U.S. Gov't