title: A presumed missense mutation of RPGR causes abnormal RNA splicing with exon skipping.
abstract: OBJECTIVE
  A patient with retinitis pigmentosa demonstrated a novel RPGR mutation (213G>A, last base of exon 2) predicted to cause a missense change (G52R) in the final protein. This study was performed to determine whether this mutation altered the effectiveness of the adjacent splice site.
  
  
  METHODS
  Observational case report.
  
  
  METHODS
  Total RNA was extracted from leukocytes of the proband and his carrier mother. Reverse transcription-polymerase chain reaction (RT-PCR) was performed by using the primers flanking exon 2 of RPGR transcript, followed by gel purification and direct sequencing.
  
  
  RESULTS
  Sequencing revealed skipping of exon 2 in the mutated transcript, leading to in-frame deletion of 42 amino acids affecting the critical RCC1-like domain.
  
  
  CONCLUSIONS
  The last base of exons is conserved as "G" in 80% of splicing consensus sequences, yet when changed, can completely disrupt constitutive splicing as in this patient. Our data confirm that the evaluation of the effects of some DNA sequence alterations at the RNA level might have important implications for appropriate genotype-phenotype correlations.
authors.affiliation: Department of Ophthalmology, School of Medicine, 203 Lothrop Street, Room 1027, Pittsburgh, PA 15213, USA. demirciyk@upmc.edu
authors.forename: F Yesim K
authors.initials: FY
authors.lastname: Demirci
authors.forename: Amy L
authors.initials: AL
authors.lastname: Radak
authors.forename: Brian W
authors.initials: BW
authors.lastname: Rigatti
authors.forename: Tammy S
authors.initials: TS
authors.lastname: Mah
authors.forename: Michael B
authors.initials: MB
authors.lastname: Gorin
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D005091:Exons / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D012150:Polymorphism, Restriction Fragment Length; D012326:RNA Splicing / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D005136:Eye Proteins; D020662:Guanine Nucleotide Exchange Factors; C099929:RPGR protein, human