Linked Life Data

15108204

Source:http://linkedlifedata.com/resource/pubmed/id/15108204

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-4-26
pubmed:abstractText
We have characterized the molecular basis of beta-hexosaminidase A (HEX A) deficiency in a patient ascertained through an ophthalmologic examination that revealed cherry red spots on his retina. The absence of neurological deficit in this child until 3 3/4 years of age indicated residual HEX A must be present. Three HEXA mutations, 10T > C (S4P) and 972T > A (V324V) on the maternal allele, and 1A > T (M1L) on the paternal allele were identified. The effects of the amino acid substitutions on HEX A expressed in COS-7 cells were analyzed; as expected, no HEX A activity was associated with the M1L mutation but surprisingly, the S4P mutation resulted in 59% of the HEX A activity expressed by the wild type cDNA. The effect of the S4P change was much less than that of another HEXA mutation, G269S, associated with an adult onset form of G(M2) gangliosidosis. This indicated that the S4P change was not the cause of disease and suggested that one of the mutations on the maternal allele, 10T > C or 972T > A, had its effect at the mRNA level. This was confirmed by Northern blot analysis that showed only 7% of the normal level of HEXA mRNA in proband fibroblasts. Analysis of the residual mRNA by RT/PCR and sequencing revealed normal transcripts from both the maternal and paternal allele, as well as a low abundance aberrant transcript from the maternal allele. Sequencing of this aberrant transcript revealed a new exon 8 donor site created by the 972T > A mutation that resulted in a 17 bp deletion and destabilization of the resulting abnormal transcript. The remaining normal mRNA produced from the 972T > A allele must account for the delayed onset of clinical symptoms in this child.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1552-4825
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
127A
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
158-66
pubmed:dateRevised
2008-5-21
pubmed:meshHeading
pubmed-meshheading:15108204-Alternative Splicing, pubmed-meshheading:15108204-Animals, pubmed-meshheading:15108204-Base Sequence, pubmed-meshheading:15108204-Blotting, Northern, pubmed-meshheading:15108204-Blotting, Western, pubmed-meshheading:15108204-COS Cells, pubmed-meshheading:15108204-Cercopithecus aethiops, pubmed-meshheading:15108204-DNA Primers, pubmed-meshheading:15108204-Fatal Outcome, pubmed-meshheading:15108204-Fibroblasts, pubmed-meshheading:15108204-Gangliosidoses, GM2, pubmed-meshheading:15108204-Hexosaminidase A, pubmed-meshheading:15108204-Humans, pubmed-meshheading:15108204-Infant, pubmed-meshheading:15108204-Mutation, pubmed-meshheading:15108204-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:15108204-RNA, Messenger, pubmed-meshheading:15108204-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15108204-Sequence Analysis, DNA, pubmed-meshheading:15108204-beta-N-Acetylhexosaminidases
pubmed:year
2004
pubmed:articleTitle
Severe subacute GM2 gangliosidosis caused by an apparently silent HEXA mutation (V324V) that results in aberrant splicing and reduced HEXA mRNA.
pubmed:affiliation
Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E OW3, Canada.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't