title: Oculopharyngeal muscle dystrophy: fine structure and mRNA expression levels of PABPN1.
abstract: OBJECTIVE
  The underlying molecular mechanism leading to the OPMD causing mutation in the PABPN1 gene has not been elucidated so far. Two models are under consideration: the first model is the polymerase slippage mechanism. The second model is unequal crossing over. The aim of the present study is to correlate clinical, fine structural, and molecular genetic data.
  
  
  METHODS
  In 6 cases of OPMD, confirmed by electron microscopy, we analyzed mutations in exon 1 of the polyadenine binding protein nuclear1 (PABPN1) gene on chromosome 14q11.1 using DNA isolated from biopsied muscle tissue. Furthermore, the corresponding mRNA from frozen biopsies was analyzed.
  
  
  RESULTS
  In addition to the usual expansion of the (GCG)6 sequence to the well known (GCG)8-13 trinucleotide repeats in 5 of the patients, we detected a novel (GCA)2(GCG) insertion in one patient. This mutation favors a pathomechanism of "unequal crossing over" instead of a "polymerase slippage" model. Tubulofilamentous (8.5 nm) nuclear inclusions were especially prominent in an isolated nucleus of a nuclear clump in a severely atrophic muscle fiber. However, no correlation was found between muscle weakness, the frequency of repeats, and the frequency and size of nuclear inclusions.
  
  
  CONCLUSIONS
  Muscle weakness was not obviously correlated to the number of repeats, but it is suggested that it might be linked to an increase of the transcription rate representing the ratio between mutated versus normal RT-PCR products.
authors.affiliation: Department of Neuropathology, University Hospital, RWTH Aachen, Germany. jmschroder@ukaachen.de
authors.forename: J M
authors.initials: JM
authors.lastname: Schröder
authors.forename: T
authors.initials: T
authors.lastname: Klossok
authors.forename: J
authors.initials: J
authors.lastname: Weis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000235:genetics / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D018908:Muscle Weakness / Q000235:genetics; D018482:Muscle, Skeletal / Q000648:ultrastructure; D039141:Muscular Dystrophy, Oculopharyngeal / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D039103:Poly(A)-Binding Protein II / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019680:Trinucleotide Repeat Expansion
chemical_list: D039103:Poly(A)-Binding Protein II; D012333:RNA, Messenger