II: 4
Case# Zhong 2:4, Male, China
CasePresentingHPOs HP:0007675, HP:0000580, HP:0007994, HP:0100019
CasePreviousTesting Yes, genome wide scan, exons 1-22
CaseMethod1 WES
CaseMethod2 Sanger
Variant NM_004698.2:c.1345C>G
CAID CA342279767
CasePMIDs 21281067
c.1532A > C
Case# Zhong 3:2, Male, China
CasePresentingHPOs (HP:0007675, HP:0000580, HP:0007994, HP:0100019) no?
CasePreviousTesting no
CaseMethod1 WES
CaseMethod2 Sanger
Variant NM_004698.2:c.1532A>C
CAID CA342282924
HPRP3
Case# Chakarova P, European
CasePresentingHPOs HP:0007675, HP:0001133
CasePreviousTesting no
CaseMethod1 PCR
CaseMethod2 DHPLC and direct sequencing
Variant NM_004698.3(PRPF3):c.1477C>T (p.Pro493Ser)
ClinVar 3353
CasePMIDs 16799052
Figure 5.
NonHumanModel Mus musculus
GeneAlteration oligonucleotide-directed mutagenesis of lambda phage to make a p.T494M vector to inject mice.
ModelPhenotype HP:0031531
HumanPhenotype HP:0000572
ModelEvidence Electron microscopy of retina showed degeneration of RPE indicated by abnormal basal morphology (fig. 5)
ModelVariant NM_004698.3(PRPF3):c.1481C>T (p.Thr494Met), 3352
III:9
Case# Meng 3:9, Male, 80, China
CasePresentingHPOs HP:0007675, HP:0100019
CaseMethod1 Sanger
CaseMethod2 NGS
CaseGenotypingMethod "NGS on all exons of 47 known retinal dystrophy associated genes"
Variant NM_004698.3(PRPF3):c.1481C>T (p.Thr494Met)
ClinVar 3352
new mutation in PRPF3 in a Spanish adRP family
Case# Gamundi II:6, female, Spanish
CasePresentingHPOs HP:0007843, HP:0007791, HP:0007675
CasePreviousTesting no
CaseMethod1 PCR
CaseGenotypingMethod scanned cDNA
Variant NM_004698.3(PRPF3):c.1466C>A (p.Ala489Asp)
ClinVar 3354
gnomAD n/a
VariantEvidence n/a
Figure 3
NonPatientCell UBERON:0005424, "ARPE19 cells"
GOterm GO:0042802
GeneAlteration HD-Ad-F3iT494M was constructed by introducing the HA-tagged PRPF3 coding sequence carrying T493M mutation, under control of the Ubiquitin C promoter and followed by the bovine growth hormone poly(A) signal, into HD-Ad-F3i.
FunctionalEvidence T494M phosphorylates less readily than WT
FAVariants NM_004698.3(PRPF3):c.1481C>T (p.Thr494Met), 3352
Figure 1
NonPatientCell UBERON:0005424
GOterm GO:0042802
GeneAlteration shRNAs cloned into pCAG-mir30 vector that contained a puromycin resistance gene.
FunctionalEvidence electron microscopy of RPE in 1-2 yo mice showed 37-48% reduced phagocytosis in mutants. (fig. 1) Assayed cryosection of mouse RPE showed mislocalization of adhesion/phagocytosis markers in RPE (fig. 4)
FAVariants NM_004698.3(PRPF3):c.1481C>T (p.Thr494Met), 3352