title: Variant haploinsufficiency and phenotypic non-penetrance in PRPF31-associated retinitis pigmentosa.
abstract: Retinitis pigmentosa (RP) is a genetically heterogenous group of inherited disorders, characterized by death of the retinal photoreceptor cells, leading to progressive visual impairment. One form of RP is caused by mutations in the ubiquitously expressed splicing factor, PRPF31, this form being known as RP11. An intriguing feature of RP11 is the presence of non-penetrance, which has been observed in the majority of PRPF31 mutation-carrying families. In contrast to variable expressivity, which is highly pervasive, true non-penetrance is a very rare phenomenon in Mendelian disorders. In this article, the molecular mechanisms underlying phenotypic non-penetrance in RP11 are explored. It is an elegant example of how our understanding of monogenic disorders has evolved from studying only the disease gene, to considering a mutation on the genetic background of the individual - the logical evolution in this genomic era.
authors: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors: A M
authors: AM
authors: Rose
authors: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors: S S
authors: SS
authors: Bhattacharya
mesh_terms: D000483:Alleles; D016923:Cell Death; D002888:Chromosomes, Human, Pair 19; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005787:Gene Frequency; D057895:Haploinsufficiency; D006801:Humans; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051117:Scavenger Receptors, Class A / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C466622:CNOT3 protein, human; D005136:Eye Proteins; C495139:MSR1 protein, human; C454222:PRPF31 protein, human; D051117:Scavenger Receptors, Class A; D014157:Transcription Factors
keywords: MSR1; PRPF31; epistasis; incomplete penetrance; non-penetrance; phenotype; repeat elements; retinal degeneration; retinitis pigmentosa