title: A large deletion in the adRP gene PRPF31: evidence that haploinsufficiency is the cause of disease.
abstract: OBJECTIVE
  To report a large deletion that encompasses more than 90% of PRPF31 gene and two other neighboring genes in their entirety in an adRP pedigree that appears to show only the typical clinical features of retinitis pigmentosa.
  
  
  METHODS
  To identify PRPF31 mutation in a dominant RP family (ADRP2) previously linked to the RP11 locus, the 14 exons of PRPF31 were screened for mutations by direct sequencing. To investigate the possibility of a large deletion, microsatellite markers near PRPF31 gene were analyzed by non-denaturing PAGE.
  
  
  RESULTS
  Initial screening of PRPF31 gene in the ADRP2 family did not reveal an obvious mutation. A large deletion was however suspected due to lack of heterozygosity for nearly all PRPF31 intragenic single nucleotide polymorphysm (SNPs). In order to estimate the size of the deletion, SNPs and microsatellite markers spanning and flanking PRPF31 were analyzed in the entire ADRP2 family. Haplotype analysis with the above markers suggested a deletion of approximately 30 kb that included the putative promoter region of a novel gene OSCAR, the entire genomic content of genes NDUFA3, TFPT and more than 90% of PRPF31 gene. Sequence analysis of the region flanking the potential deletion showed a high presence of Alu elements implicating Alu mediated recombination as the mechanism responsible for this event.
  
  
  CONCLUSIONS
  This mutation provides evidence that haploinsufficiency rather than aberrant function of mutated proteins is the cause of disease in these adRP patients with mutations in PRPF31 gene.
authors.affiliation: Institute of Ophthalmology, University College London, London, UK.
authors.forename: Leen
authors.initials: L
authors.lastname: Abu-Safieh
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.forename: Irmela
authors.initials: I
authors.lastname: Mantel
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.forename: Lucia
authors.initials: L
authors.lastname: Pelosini
authors.forename: Alan C
authors.initials: AC
authors.lastname: Bird
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005799:Genes, Dominant; D006239:Haplotypes; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D009245:NADH Dehydrogenase; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D042967:Electron Transport Complex I; D005136:Eye Proteins; D009245:NADH Dehydrogenase; D011956:Receptors, Cell Surface; C510270:NDUFA3 protein, human; C512828:OSCAR protein, human; C454222:PRPF31 protein, human; C118089:TFPT protein, human