Variant haploinsufficiency and phenotypic non‐penetrance in PRPF31‐associated retinitis pigmentosa

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 know...

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Bibliographic Details
Published in:Clinical genetics 2016-08, Vol.90 (2), p.118-126
Main Authors: Rose, A.M., Bhattacharya, S.S.
Format: Article
Language:English
Subjects:
Alleles
Cell Death
Chromosomes, Human, Pair 19
epistasis
Eye diseases
Eye Proteins - genetics
Eye Proteins - metabolism
Gene Expression Profiling
Gene Expression Regulation
Gene Frequency
Genetic disorders
Haploinsufficiency
Humans
incomplete penetrance
MSR1
Mutation
non‐penetrance
Pedigree
Penetrance
Phenotype
Promoter Regions, Genetic
PRPF31
repeat elements
Retinal Cone Photoreceptor Cells - metabolism
Retinal Cone Photoreceptor Cells - pathology
retinal degeneration
Retinal Rod Photoreceptor Cells - metabolism
Retinal Rod Photoreceptor Cells - pathology
retinitis pigmentosa
Retinitis Pigmentosa - genetics
Retinitis Pigmentosa - metabolism
Retinitis Pigmentosa - pathology
Scavenger Receptors, Class A - genetics
Scavenger Receptors, Class A - metabolism
Signal Transduction
Transcription Factors - genetics
Transcription Factors - metabolism
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Description
Summary: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.
ISSN:0009-9163
1399-0004
DOI:10.1111/cge.12758