Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients
Abstract
:1. Introduction
2. Results
2.1. Syndromic and Non-Syndromic USH2A-RP
2.2. Truncating USH2A Variants were More Frequently Detected in Syndromic than Non-Syndromic USH2A-RP Patients
2.3. Earlier Onset of RP in Syndromic Patients than Non-Syndromic USH2A-RP Patients
2.4. Visual Acuity and Visual Field Constriction in Syndromic and Non-Syndromic USH2A-RP Patients
3. Discussion
4. Materials and Methods
4.1. Ethical Statement
4.2. Patients Recruitment or Inclusion Criteria
4.3. Genetic Analysis
4.4. Clinical Evaluations
4.5. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
RP | Retinitis Pigmentosa |
IRD | Inherited Retinal Degenerative Disease |
USH2A-RP | USH2A-associated RP |
HFA | Humphrey field analyzer |
MD | Mean Deviation |
References
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ID | Nucleotide Change | Protein Change | Zygosity |
---|---|---|---|
P1 | c.490G>T;c.13631dupG | p.(Val164Phe);p.(Pro4545Serfs*17) | Het;Het |
P2 | c.1923T>A;c.3958C>T;c.5396delA | p.(Cys641*);p.(Pro1320Ser) 1;p.(Lys1799Serfs*18) | Het;Het;Het |
P3 | c.13576C>T;c.13847G>T | p.(Arg4526*);p.(Gly4616Val) | Homo;Homo |
P4 | c.2653C>T;c.9751T>C; c.13576C>T;c.13847G>T | p.(His885Tyr) 2; p.(Cys3251Arg) 2;p.(Arg4526*)2;p.(Gly4616Val)2 | Het;Het; Het;Het |
P5 | c.8559-2A>G;c.14133+2T>A | p.(?);p.(?) | Het;Het |
P6 | c.8396delG | p.(Gly2799Valfs*31) | Homo |
P7 | c.10353_10356delTCAT;c.13010C>T | p.(His3452Glnfs*4);p.(Thr4337Met) | Het;Het |
P8 | c.2802T>G;c.5158delC | p.(Cys934Trp);p.(Leu1720*) | Het;Het |
P9 | c.8559-2A>G;c.10712C>T | p.(?);p.(Thr3571Met) | Het;Het |
P10 | c.8559-2A>G;c.14004delG | p.(?);p.(Leu4668Phefs*10) | Het;Het |
P11 | c.8559-2A>G | p.(?) | Homo |
P12 | c.10859T>C;c.11328T>G | p.(Ile3620Thr);p.(Tyr3776*) | Het;Het |
P13 | c.14243C>T | p.(Ser4748Phe) | Homo |
P14 | c.3596_3598delAAG;c.8254G>A | p.(Glu1199del);p.(Gly2752Arg) | Het;Het |
P15 | c.662C>A;c.7068T>G;c.7234G>A | p.(Thr221Lys) 1;p.(Asn2356Lys);p.(Val2412Met) 1 | Het;Het;Het |
P16 | c.490G>T;c.3595_3597delGAA | p.(Val164Phe);p.(Glu1199del) | Het;Het |
P17 | c.10859T>C;c.14766G>A | p.(Ile3620Thr);p.(Trp4922*) | Het;Het |
P18 | c.8559-2A>G;c.14243C>T | p.(?);p.(Ser4748Phe) | Het;Het |
P19 | c.11156G>A;c.13010C>T | p.(Arg3719His);p.(Thr4337Met) | Het;Het |
P20 | c.2802T>G;c.13847G>T | p.(Cys934Trp);p.(Gly4616Val) | Het;Het |
P21 | c.(11712_12066)del;c.15233C>G | p.(?);p.(Pro5078Arg) | Het;Het |
P22 | c.8254G>A | p.(Gly2752Arg) | Homo |
P23 | c.850G>A;c.2802T>G | p.(Glu284Lys);p.(Cys934Trp) | Het;Het |
P24 | c.4310_4312dupATA;c.8254G>A | p.(Tyr1437_Arg1438insAsn);p.(Gly2752Arg) | Het;Het |
P25 | c.6399G>A;c.13887G>T | p.(Trp2133*);p.(Glu4629Asp) | Het;Het |
P26 | c.2802T>G;c.9815C>T | p.(Cys934Trp);p.(Pro3272Leu) | Het;Het |
P27 | c.14243C>T;c.15233C>G | p.(Ser4748Phe);p.(Pro5078Arg) | Het;Het |
P28 | c.9371+1G>T;c.12094G>A | p.(?);p.(Gly4032Arg) | Het;Het |
P29 | c.3596_3598delAAG;c.8254G>A;c.13894C>G | p.(Glu1199del);p.(Gly2752Arg);p.(Pro4632Ala)1 | Het;Het;Het |
P30 | c.685G>C;c.13708C>T | p.(Gly229Arg);p.(Arg4570Cys) | Het;Het |
P31 | c.8254G>A;c.8396delG | p.(Gly2752Arg);p.(Gly2799Valfs*31) | Het;Het |
P32 | c.2802T>G;c.11811_11812delCT | p.(Cys934Trp);p.(Tyr3938Argfs*8) | Het;Het |
P33 | c.490G>T;c.12383A>G | p.(Val164Phe);p.(Tyr4128Cys) | Het;Het |
P34 | c.2609G>T;c.5608C>T; c.12305T>A;c.15355C>T | p.(Cys870Phe) 1;p.(Arg1870Trp); p.(Ile4102Asn) 1;p.(Arg5119Trp)1 | Het;Het; Het;Het |
P35 | c.10495C>T;c.10712C>T | p.(Pro3499Ser);p.(Thr3571Met) | Het;Het |
P36 | c.8339T>A;c.12407C>T | p.(Val2780Asp);p.(Thr4136Ile) | Het;Het |
Characteristics | Syndromic RP 1 | Non-Syndromic RP 2 | |
---|---|---|---|
Age (years, mean ± SD, range) | 48.5 ± 12.9, 27–69 | 50.9 ± 15.7, 26–82 | |
Gender (n, %) | Male | 6 (54.5) | 13 (52.0) |
Family History (n, %) | Yes | 5 (45.5) | 6 (24.0) |
Consanguineous Marriage (n, %) | Yes | 1 (9.1) | 2 (8.0) |
Type of Variant | Syndromic RP 1 | Non-Syndromic RP 2 |
---|---|---|
Truncating / Truncating (n, %) | 6 (54.5) | 0 (0.0) |
Truncating / Missense (n, %) | 5 (45.5) | 8 (32.0) |
Missense / Missense (n, %) | 0 (0.0) | 17 (68.0) |
USH2A Variants | Syndromic RP 1 | Non-Syndromic RP 2 |
---|---|---|
p.(Val164Phe) | 1 | 2 |
p.(Cys934Trp) | 1 | 4 |
p.(Glu1199del) | 0 | 3 |
p.(Gly2752Arg) | 0 | 5 |
p.(Gly2799Valfs*31) | 1 | 1 |
c.8559-2A>G | 4 | 1 |
p.(Thr3571Met) | 1 | 1 |
p.(Ile3620Thr) | 0 | 2 |
p.(Ser4748Phe) | 0 | 3 |
p.(Thr4337Met) | 1 | 1 |
p.(Arg4526*) | 2 | 0 |
p.(Gly4616Val) | 2 | 1 |
p.(Pro5078Arg) | 0 | 2 |
Phenotype | Patient | Rate of Changes in MD Values | Observation Period (Years) |
---|---|---|---|
syndromic RP | P8 | −1.54 | 1 |
non-syndromic RP | P12 | −0.67 | 8 |
P25 | −0.88 | 1 | |
P27 | −0.65 | 6 | |
P33 | −0.48 | 2 | |
P36 | −0.34 * | 6 |
ABCA4 | BEST1 | BBS1* | C2orf71 | CEP290* |
CDH23 * | CDHR1 * | CHM * | CNGA1 | CNGB1 |
CNGB3 | CRB1 | CRX | CYP4V2 | EYS |
FAM161A * | GPR98 * | GUCA1A * | GUCY2D | IMPDH1 |
IMPG2 | KLHL7 * | LRAT | MAK | MERTK |
MYO7A * | NR2E3 | NRL | PCDH15 * | PDE6B |
PRCD | PROM1 | PRPF31 | PRPF6 | PRPH2 |
RDH5 | RDH12 | RHO | ROM1 | RP1 |
RP1L1 | RP2 | RP9 | RPE65 | RPGR |
RS1 * | SNRNP200 | TOPORS | TULP1 | USH2A |
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Inaba, A.; Maeda, A.; Yoshida, A.; Kawai, K.; Hirami, Y.; Kurimoto, Y.; Kosugi, S.; Takahashi, M. Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients. Int. J. Mol. Sci. 2020, 21, 7817. https://doi.org/10.3390/ijms21217817
Inaba A, Maeda A, Yoshida A, Kawai K, Hirami Y, Kurimoto Y, Kosugi S, Takahashi M. Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients. International Journal of Molecular Sciences. 2020; 21(21):7817. https://doi.org/10.3390/ijms21217817
Chicago/Turabian StyleInaba, Akira, Akiko Maeda, Akiko Yoshida, Kanako Kawai, Yasuhiko Hirami, Yasuo Kurimoto, Shinji Kosugi, and Masayo Takahashi. 2020. "Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients" International Journal of Molecular Sciences 21, no. 21: 7817. https://doi.org/10.3390/ijms21217817