Table 2.
Variant assessment of the identified MFRP and PRSS56 mutations in 21 unrelated families with NNO or MCOP.
| FAM. PID | Diagnosis | Gene | cDNA | Protein | Geno-type | Exon | Segregation | Grantham distance | SIFT | PolyPhen-2 | GVGD | Mutation Taster | gnomAD (Total population frequency) | ACMG Classifi-cation | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
F1. |
NNO/RP | MFRP | c.1090_1094del | p.(Thr364Glnfs*26) | HOM | 9 | NP | / | / | / | / | / |
0.0004102% (0 HOM) |
Class 4 | This study |
|
F2. |
MCOP | MFRP | c.498del | p.(Asn167Thrfs*25) | HOM | 5 | Yes | / | / | / | / | / |
0.0004024% (0 HOM) |
Class 5 | 20,38,44,45,52 |
|
F3. GC19623 |
MCOP | MFRP | c.1549C > T | p.(Arg517Trp) | HOM | 13 | NP | 101 | D |
Prob. dam. |
C25 |
Dis. caus. |
0.002022% (0 HOM) |
Class 4 | 41 |
|
F4. GC19691 |
MCOP | MFRP |
c.491_492insT 2nd variant unknown |
p.(Asn167Glnfs*34) | HTZ | 5 | NP | / | / | / | / | / |
0.005723% (0 HOM) |
Class 5 | 36 |
|
F5. |
NNO/ RP |
MFRP | c.498dup | p.(Asn167Glnfs*34) | HOM | 5 | NP | / | / | / | / | / |
0.005723% (0 HOM) |
Class 5 | 8,36,41 |
|
F6. GC18886 |
MCOP/ RP |
MFRP | c.1231T > C | p.(Tyr411His) | HOM | 10 | NP | 83 | D |
Prob. dam. |
C0 |
Dis. caus. |
Absent | Class 3 | This study |
|
F7. GC20271 |
MCOP/ RP |
MFRP | c.955C > T | p.(Gln319*) | HTZ | 8 | / | / | / | / | / | / | Absent | Class 5 | This study |
| c.6087_54 +40delinsTAGTGGT | none | HTZ | 5′UTR & 1 | / | / | / | / | / | / | Absent | ? | This study | |||
|
F8. |
NNO/ RP |
MFRP | c.498del | p.(Asn167Thrfs*25) | HOM | 5 | NP | / | / | / | / | / |
0.0004024% (0 HOM) |
Class 5 | 36,39,42,48 |
|
F9. |
MCOP | MFRP | c.1090_1094del | p.(Thr364Glnfs*26) | HOM | 9 | Yes | / | / | / | / | / |
0.0004102% (0 HOM) |
Class 5 | This study |
|
F10. |
NNO | MFRP | c.498del | p.(Asn167Thrfs*25) | HOM | 5 | Yes | / | / | / | / | / |
0.0004024% (0 HOM) |
Class 5 | 36,39,42,48 |
|
F11. GC20258 |
MCOP | PRSS56 | c.833dup | p.(Val279Argfs*2) | HTZ | 7 | NP | / | / | / | / | / | Absent | Class 5 | 49 |
| c.1571del | p.(Val525Cysfs*55) | HTZ | 13 | NP | / | / | / | / | / | Absent | Class 5 | This study | |||
|
F12. GC18588 |
MCOP | PRSS56 | c.1066dupC | p.(Gln356Profs*152) | HOM | 9 | NP | / | / | / | / | / | Absent | Class 5 | 17,51,53 |
|
F13. GC16899 |
MCOP | PRSS56 | c.320G > A | p.(Gly107Glu) | HOM | 4 | NP | 98 | D |
Poss. dam. |
C25 |
Dis. caus. |
0.009375% (0 HOM) |
Class 3 | This study |
|
F14. GC19721 |
MCOP | PRSS56 | c.1555G > C | p.(Gly519Arg) | HOM | 13 | NP | 125 | D |
Prob. dam. |
C0 |
Dis. caus. |
Absent | Class 4 | 53 |
|
F15. RXK4624916 |
MCOP/ RP |
PRSS56 | HOM | Yes | |||||||||||
|
F15. RXK3297132 |
MCOP/ RP |
HOM | |||||||||||||
|
F15. RXK33447157 |
MCOP | HOM | |||||||||||||
|
F15. RXK3113374 |
MCOP | HOM | |||||||||||||
|
F15. RXK4633376 |
MCOP | HOM | |||||||||||||
|
F16. RXK4941281 |
MCOP | PRSS56 | HOM | Yes | |||||||||||
|
F17. RXK4985235 |
MCOP | PRSS56 | HOM | Yes | |||||||||||
|
F18. |
MCOP | PRSS56 | c.766T > C | p.(Cys256Arg) | HOM | 7 | Yes | 180 | D |
Prob. dam. |
C0 |
Dis. caus. |
Absent | Class 4 | This study |
|
F19. |
NNO | PRSS56 | c.766T > C | p.(Cys256Arg) | HOM | Yes | |||||||||
|
F20. |
NNO | / | / | / | / | / | / | / | / | / | / | / | / | / | / |
|
F21. |
NNO | / | / | / | / | / | / | / | / | / | / | / | / | / | / |
Abbreviations used: FAM. PID: Family. Patient ID; HOM: homozygous; HTZ: heterozygous; NNO: isolated nanophthalmos; MCOP: isolated posterior microphthalmia; RP: retinitis pigmentosa; MCOP/RP: posterior microphthalmia with RP; NNO/RP: nanophthalmos with RP; /: no mutation identified; NP: not performed; D: deleterious; Prob. Dam.: probably damaging; Poss. Dam.: possibly damaging; Dis. Caus.: disease causing; Class 3: uncertain significance; Class 4: likely pathogenic; Class 5: pathogenic.