Table 3. Rare LRP5 variants identified in advanced retinopathy of prematurity patients.
| Location | cDNA change | Protein change (score with Blosum62) | Occurrence in patients | Allele frequency in ethnically matched samples | Known polymorphism (rs ID, allele frequency) | Computational analysis score |
Patient characteristics: ethnicity; gender; birthweight; gestational age; clinical data | Reference | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| SIFT | Poly- phen2 | Mutation Taster | Phylop | ||||||||
| Exon 17 |
c.3656G>A |
p.R1219H (0) |
1/53 |
NA |
Yes
(rs143924910, 0.022%) |
0.59 (T) |
0.996 (PrD) |
0.9988 (Dc) |
0.9904 (C) |
#N5701: Japanese; male; 864 g; 26 gw; Classic ROP, Stage 4A (OU), Lx at 8 w, Vx at 13 w |
This study |
| Exon 20 |
c.4148A>C |
p.H1383P (−2) |
1/53 |
1/386 |
No |
0.26 (T) |
0.001 (B) |
0.9983 (Dc) |
0.9975 (C) |
#N1701: Japanese; female; 719 g; 25 gw; Classic ROP, Stage5 (OD), Stage 4B (OS), Lx (OU), Vx at 6 m (OD) and 4 y (OS) |
This study |
| Exon 23 | c.4619C>T | p.T1540M (−1) | 1/53 | 4/386 | Yes (rs141407040, 0.022%) | 0 (D) | 1.00 (Prd) | 0.9908 (Dc) | 0.9617 (C) | #N1001: Japanese; male; 850 g; 25 gw; Classic ROP, Stage 4B (OS) / 5(OD), Lx (OU), Vx at 6 m (OU) | This study |
Allele frequency from ethnically-matched samples was obtained from random individuals. Known polymorphism was based on the dbSNP, and the allele frequency was on the Exome Variant Server, NHLBI Exome Sequencing Project (ESP), Seattle, WA. Computational analyses were performed by 4 programs (SIFT, Polyphen2, Mutation taster, and PhyloP). Pathogenic results are shown by bold characters as “D (damaging)” for SIFT, “PrD (probably damaging)” or “PsD (possibly damaging)” for Polyphen2, “Dc (disease-causing)” for Mutation Taster, and “C (conserved)” for PhyloP. Non-pathogenic results are shown by italic characters as “T (tolerated)” for SIFT, and “B (benign)” for Polyphen2. g: gram, gw: gestational weeks, Lx: laser, m: months after birth, NA: not analyzed, Vx: vitrectomy, y: years after birth.