Table 1 Clinical and genetic findingsin the index patients of the likely characterized families.
Family (index) | Onset age: First symptom Extraction age: Symptoms | Fundus examination | Clin. Diagn. | Gene | [Allele 1] | [Allele 2] | Clin. Significance (Known v.)* | Segr An. | Other features and comments |
|---|---|---|---|---|---|---|---|---|---|
Reference | Reference | Pathog. Scores (Novel v.)** | |||||||
A (II:1) | 10y: VAD. 34y: VA CF; NB; VFR; CVA; | Macular pigment deposits | STGD | ABCA4 | M1: c.4253 + 5G > A; r.(spl?)68 | M2: c.5898G > A; r.(spl?) p.Glu1966Glu This study | M1 Clinvar: Pathog. | Yes | Photoph. |
M2 MT: Damaging NNS: Donor Lost HSF: Site Broken | |||||||||
B (II:1) | 2y: Intense photoph. 5y: VAD; CVA. | No apparent changes | COD | CNGB3 | M3: c.1148del; p.Thr383Ilefs*1353 | M3 Clinvar: CIP [Pathog.(14); VUS(1)] | Yes | Consang.; Micronystagmus; Amblyopia; Hypermetropia | |
ABCA4 | m4: c.466A > G; p.Ile156Val (†)44 | m4 Clinvar: VUS | — | ||||||
C (II:1) | 40y: NB 69y: VFC.; VAD. | Typical of RP at a later stage; RPE atrophy | sRP | FSCN2 | m5: c.1345 + 6_1345 + 10dup; r.(spl?); This study | m5 MT: Damaging NNS: No changes HSF: No impact | NA | Catar. | |
ABCA4 | m6: c.6148G > C; p.Val2050Leu (†)69 | m6 Clinvar: CIP [Ben.(1); Likely ben.(4); Likely pathog.(3); Pathog.(1)] | NA | ||||||
D (II:1) | 1y: NB 29y: Ring scotoma; VAD; CVA. | Punctate yellow-white deposits in the macula; Peripapillary atrophy | LCA | LRAT | M7: c.163C > G; p.Arg55Gly This study | M7 MT: Damaging SIFT: Damaging Polyph: Damaging | Yes | Photoph.; Consang. | |
E (II:4) | 18y: NB 24y: Tunnel vision (central island, 30°) | RPE atrophy, bone spicule pigmentation | sRP | USH2A | M8: c.1560C > A; p.Cys520* This study | M9: c.2276G > T; p.Cys759Phe (†)62 | M8 MT: Damaging | NA | None |
M9 Clinvar: CIP [Likely pathog.(6); Pathog.(7); VUS(2)] | |||||||||
USH2A | m10: c.6590 C > T; p.Thr2197Ile20 | m10 Clinvar: CIP [Likely Pathog.(1); VUS(1)] | NA | ||||||
F (II:3) | 25y: NB 39y: VFC; Discrete VAD. | Bone spicule pigmentation in the periphery | sRP | USH2A | M11: c.2167 + 5G > A; r.(spl?)70 | M9: c.2276G > T; p.Cys759Phe (†)62 | M11 Clinvar: Pathog71 | NA | Myopia; Astigmatism |
M9: see above | |||||||||
G (II:1) | 18y: VF constr. 48y: NB; Tunnel vision; VAD | Typical of RP | sRP | USH2A | M9: c.2276G > T; p.Cys759Phe (†)62 | M12: c.12574 C > T; p.Arg4192Cys72 | M9: see above | NA | Incipient catar.; Tritanopia |
M12 Clinvar: CIP [Likely pathog.(2); VUS(1) | |||||||||
H (II:3) | 12y: NB 33y: VFC.; VAD; CVA | Bone spicule pigmentation in the periphery | arRP + SNHL | USH2A | M9: c.2276G > T; p.Cys759Phe (†)62 | M13: c.12457del; p.Ala4153Profs*14 | M9: see above | Yes | Progressive and bilateral SNHL (33y); Father with SNHL. Brother with isolated arRP |
M13 HGMD: Pathog. | |||||||||
I (II:2) | 30y: VF constr. 50y: NB; VF island 5° central; VAD | Typical of RP | sRP | USH2A | M9: c.2276G > T; p.Cys759Phe (†)62 | M14: c.9799T > C; p.Cys3267Arg73 | M9: see above | NA | Catar.; Photoph. |
M14 Clinvar: Likely pathog. | |||||||||
J (II:1) | 19y: NB 30y: VFC. | Typical of RP | sRP | USH2A | M9: c.2276G > T; p.Cys759Phe(†)62 | M15: c.11156G > A; p.Arg3719His72 | M9: see above | NA | None |
M15 Clinvar: Pathog. | |||||||||
K (II:1) | 12y: NB and VFR. 15y: VF Central island, 10° | Decrease in retinal thickness; No bone-spicule pigmentation | sRP (sp) | USH2A | M9: c.2276G > T; p.Cys759Phe (†)62 | M16: c.14011G > T; p.Glu4671* This study | M9: see above | Yes | None |
M16 MT: Damaging | |||||||||
L (II:1) | 43y: NB 53y: VFC; VAD. | Typical of RP | sRP | USH2A | M9: c.2276G > T; p.Cys759Phe (†)62 | M14: c.9799T > C; p.Cys3267Arg73 | M9: see above | Yes | Catar. |
M14: see above | |||||||||
M (II:1) | 14y: NB 28y: VFC.; VAD. | Typical of RP | USH | USH2A | M17: c.2299del; p.Glu767Serfs*21 (†)74 | M18: c.15089C > A; p.Ser5030*75 | M17 Clinvar: Pathog./Likely pathog. | Yes | Nystagmus; Bilateral SNHL |
M18 LOVD: Pathog. | |||||||||
N (II:12) | 39y: VFC. 49y: NB | Typical of RP | arRP | USH2A | M17: c.2299del; p.Glu767Serfs*21 (†)74 | M19: c.4325T >C; p.Phe1442Ser76 | M17: see above | NA | Diabetes mellitus (Type II) |
M19 LOVD: Likely Pathog. | |||||||||
O (II:1) | 7y: NB 58y: Tunnel vision (5°); VAD.; CVA | Bone spicule pigmentation and pallor of the optic disc | sRP | USH2A | M20: c.907C > A; p.Arg303Ser61 | M9: c.2276G > T; p.Cys759Phe (†)62 | M20 LOVD: Likely Pathog. | NA | Photoph.;Catar.; Aphakia; Glaucoma |
M9: see above | |||||||||
P (II:9) | 13y: NB 35y: Tunnel vision (central island, 10°); VAD. | Typical of RP | USH | USH2A | M20: c.907C > A; p.Arg303Ser (†)61 | M21: Duplication Ex 46–47c.9055 + 100_9371 + 5544dup; p.? This study | M20: see above | Yes | Strabismus; Astigmatism; Photoph.;Catar.; Two sisters with isolated arRP |
M21 MT: Damaging | |||||||||
Q (II:4) | 33y: NB 34y: VFC | Typical of RP at a later stage | arRP | USH2A | M20: c.907C > A; p.Arg303Ser (†)61 | M22: c.12067–2A > G; r.spl77 | M20: see above | Yes | Incipient catar. Shiny ILM |
M22 Clinvar: Pathog. | |||||||||
R (II:6) | 10y: NB 62y: VFC; LP; Legal Blindness | Typical of RP | USH | USH2A | M23: Deletion Ex 22–55c.4628-2287_10939 + 3867del; p.? This study | M23 MT: Damaging | Yes | Catar.; Nystagmus; Bilateral SNHL | |
S (II:1) | 14y: NB 30y: VDA, VFR | Typical of RP | sRP | USH2A | m33: c.5363A > G; p.Asp1788Gly30 | m39: c.6806-810A > G; r.? m40: c.6050-8058G > C; r.? | m33 MT: Benign SIFT: Benign Polyph: Possibly Damaging | No | Myopia, astigmatism |
m39 MT: Benign NNS: New donor HSF: New Donor | |||||||||
m40 MT: Benign NNS: New acceptor HSF: New acceptor | |||||||||
