title: Aberrant splicing in the LMNA gene caused by a novel mutation on the polypyrimidine tract of intron 5.
abstract: BACKGROUND
  Familial dilated cardiomyopathy with conduction system defects variably associated with skeletal muscle abnormalities is frequently caused by LMNA gene mutations.
  
  
  METHODS
  A family affected by cardiac abnormalities, either isolated or variably associated with skeletal muscle compromise, was identified. LMNA gene analysis was applied to all family members.
  
  
  RESULTS
  A novel intron 5 (c.937-11 C > G) mutation was identified. mRNA transcription analysis was subsequently performed, and cDNA was obtained from mutated patients. It displayed an aberrant splice product featuring the insertion of 40 nucleotides from intron 5, leading to a frameshift. Computational predictions identified a cryptic splice site 40 bp upstream from the canonical site; this alternative splicing event was elicited by intronic mutation, which seems to interfere with the polypyrimidine tract of the canonical site.
  
  
  CONCLUSIONS
  We have described the first mutation on the LMNA gene interfering with the polypyrimidine tract. Our findings underline the importance of including introns in the search for mutations.
authors.affiliation: Neuromuscular Unit, Multiple Sclerosis Centre, University of Cagliari, Via Is Guaddazonis 2, Cagliari 09124, Sardinia, Italy. nikola.carboni@tiscali.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Carboni
authors.forename: Matteo
authors.initials: M
authors.lastname: Floris
authors.forename: Anna
authors.initials: A
authors.lastname: Mateddu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Porcu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marrosu
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Solla
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cocco
authors.forename: Marco
authors.initials: M
authors.lastname: Mura
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
authors.forename: Maria A
authors.initials: MA
authors.lastname: Maioli
authors.forename: Rachele
authors.initials: R
authors.lastname: Piras
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Aste
authors.forename: Maria G
authors.initials: MG
authors.lastname: Marrosu
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics*; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics*
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D038941:Polypyrimidine Tract-Binding Protein