A Combined <i>in silico</i>, <i>in vitro</i> and Clinical Approach to Characterize Novel Pathogenic Missense Variants in PRPF31 in Retinitis Pigmentosa.
One patient demonstrated an unexpected diagnosis of retinitis pigmentosa with a novel variant of unknown significance in PRPF31, and 1 showed optic nerve elevation in the setting of increased intracranial pressure (ICP) of unclear cause.
Two frameshift variants, c.547delG (p.E183fs) and c.804delG (p.L268fs), and one stopgain variant, c.1060C>T (p.R354X), in the pre-mRNA processing factor 31 gene (PRPF31) were identified in three RP families.
We hypothesize that RNA splicing factor retinitis pigmentosa will be amenable to treatment by AAV-mediated gene therapy, and that understanding the clinical progression rates of PRPF31retinitis pigmentosa will help with the design of gene therapy clinical trials.
Dominant PRPF31 mutations are hypostatic to a recessive CNOT3 polymorphism in retinitis pigmentosa: a novel phenomenon of "linked trans-acting epistasis".
Mutations in the ubiquitously expressed pre-mRNA processing factors 3, 8, and 31 (PRPF3, PRPF8, and PRPF31) cause nonsyndromic dominant retinitis pigmentosa in humans, an inherited retinal degeneration.
Two novel PRP31 premessenger ribonucleic acid processing factor 31 homolog mutations including a complex insertion-deletion identified in Chinese families with retinitis pigmentosa.
In a large adRP family, the chip allowed ruling out of all but the causative gene, and identification of an unreported null mutation (E181X) in PRPF31.
In an autosomal recessive form of RP, Bothnia dystrophy caused by mutations in the RLBP1 gene, bi-allelic mutations R234W, M226K and compound heterozygosity, M226K+R234W was detected.In dominant form of RP mapped to 19q13.42 a 59 kb genomic deletion including the PRPF31 and three other genes was found.These data provide additional information on the molecular mechanisms of RP evolvement and in the future might be useful in development of therapeutic strategies.
Similar OCT findings were present in the reported adRP patient with this ERG; the patient was heterozygous for a 4-bp deletion (Leu107del4 ctGAGT) in PRPF31.
Our results indicate that c.1374+654C>G causes retinitis pigmentosa via haploinsufficiency, similar to the vast majority of PRPF31 mutations described so far.
One family with autosomal dominant RP was found to harbor a novel truncating PRPF31 mutation (p.Phe262SerfsX59) and a known missense RHO mutation (p.Pro347Leu), and 1 affected woman was heterozygous for both mutations.