Background
Methods
Clinical diagnosis of CCRD
Molecular genetic analysis using NGS
Filtering approach
Pathogenic prediction of variants
Sanger sequencing validation and co-segregation analysis
Multiplex ligation-dependent probe amplification (MLPA) analysis for ABCA4
Copy number variations (CNVs) analysis
Results
NGS capture and coverage
Identification of pathogenic mutations
ID | Type | Consang. | Gene | NM | Allele State | Exon | cDNA | Protein | Coseg. | Conservation | Polyphen2 | Sift | Mutation taster | References |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
High confidence
| ||||||||||||||
CIC00137 | simplex |
ABCA4
| NM_000350.2 | Ho | 47 | c.6394G>A | p.(E2132K) | + | Highly | Prd | D | Dc | Novel | |
CIC00765 | Ar | + |
ABCA4
| NM_000350.2 | Ho | 47 | c.6445C>T | p.(R2149*) | + | - | - | - | - | (Lewis et al. 1999) (rs61750654) |
CIC03436 | Ar | + |
ABCA4
| NM_000350.2 | Ho | 42 | c.5892del | p.(G1965Efs*9) | Np | - | - | - | - |
a
|
CIC04412 | simplex |
ABC4A
| NM_000350.2 | Het | 34 | c.4793C>A | p.(A1598D) | + | Weakly | Pd | T | Dc | (rs61750155) [9] | |
ABCA4
| NM_000350.2 | Het | 28 | c.4234C>T | p.(Q1412*) | + | - | - | - | - | (rs61750137) [9] | |||
CIC04645 | Ar | + |
ABCA4
| NM_000350.2 | Ho | 13 | c.1924T>C | p.(F642L) | Np | Moderately | B | D | Dc | Novel, but c.1924T>A p.F642I in [80] |
CIC05087 | simplex |
ABCA4
| NM_000350.2 | Ho | IVS 11 | c.1554+1G>C | r.(spl?) | Np | Highly | - | - | - | Novel | |
CIC05853 | simplex | + |
ABC4A
| NM_000350.2 | Ho | 22 | c.3259G>A | p.E1087K | Np | Highly | Prd | D | Dc | (rs61751398) [81] |
CIC05854 | Ar | + |
ABC4A
| NM_000350.2 | Ho | 35 | c.4919G>A | p.(R1640Q) | + | Highly | Prd | D | Dc | (rs61751403) [82] |
CIC05989 | simplex |
ABC4A
| NM_000350.2 | Het | 34 | c.4837G>A | p.(D1613N) | + | Not | B | D | Dc | Novel | |
ABC4A
| NM_000350.2 | Het | 10 | c.1302del | p.(Q437Rfs*12) | + | - | - | - | - | Novel | |||
ABCA4
| NM_000350.2 | Het | 38 | c.5318C>T | p.(A1773V) | + | Moderately | Prd | D | Dc | [83] | |||
CIC06170 | simplex |
ABC4A
| NM_000350.2 | Het | 44 | c.6089G>A | p.(R2030Q) | + | Highly | Prd | D | Dc | (Lewis et al. 1999) (rs61750641) | |
ABC4A
| NM_000350.2 | Het | IVS 24 | c.3607+3A>T | r.(spl?) | + | Moderately | - | - | - | Novel | |||
ABCA4
| NM_000350.2 | Het | 14 | c.2034G>T | p.(K678N) | + | Highly | Prd | D | Dc | [84] | |||
CIC06735 | Ar | + |
ABC4A
| NM_000350.2 | Ho | 42 | c.5892del | p.(G1965Efs*9) | Np | - | - | - | - |
a
|
CIC06913 | Ar | + |
ABCA4
| NM_000350.2 | Ho | 21 | c.3056C>T | p.(T1019M) | + | Highly | Prd | D | Dc | (rs201855602) [85] |
CIC04239 | Ar | + |
CDHR1
| NM_033100.3 | Ho | 9 | c.838C>T | p.(R280*) | Np | - | - | - | Novel | |
CIC06568 | Ar | + |
CERKL
| NM_001030311.2 | Ho | 8 | c.1090C>T | p.(R364*) | Np | - | - | - | - | Thesis (Sergouniotis P. 2012) b
|
CIC07299 | simplex | + |
PDE6C
| NM_006204.3 | Ho | 2 | c.542del | p.(A181Efs*13) | Np | - | - | - | - | Novel |
CIC05218 | Ar | + |
PDE6C
| NM_006204.3 | Ho | IVS 10 | c.1413+3A>T | r.(spl?) | Np | Not | - | - | - | Novel |
CIC05563 | Ad |
SEMA4A
| NM_022367.3 | Het | 4 | c.302T>C | p.(I101T) | + | Moderately | Prd | D | Dc | Novel (rs149652495) | |
CIC07563 | simplex |
SEMA4A
| NM_022367.3 | Ho | 3 | c.241C>T | p.(R81*) | Np | - | - | - | - | Novel | |
CIC00324 | Ad |
GUCY2D
| NM_000180.3 | Het | 13 | c.2512C>T | p.(R838C) | + | Highly | Prd | D | Dc | (rs61750172) [10] | |
CIC03249 | Ad |
GUCY2D
| NM_000180.3 | Het | 13 | c.2512C>T | p.(R838C) | + | Highly | Prd | D | Dc | (rs61750172) [10] | |
CIC04347 | Ad |
GUCY2D
| NM_000180.3 | Het | 13 | c.2512C>T | p.(R838C) | + | Highly | Prd | D | Dc | (rs61750172) [10] | |
CIC04918 | Ad |
GUCY2D
| NM_000180.3 | Het | 13 | c.2512C>T | p.(R838C) | Np | Highly | Prd | D | Dc | (rs61750172) [10] | |
CIC06757 | Ad |
PRPH2
| NM_000322.4 | Het | 1 | c.514C>T | p.(R172W) | + | Moderately | Prd | D | Dc | (rs61755792) [86] | |
CIC03621 | Ad |
PRPH2
| NM_000322.4 | Het | 1 | c.1-c581+?del | - | + | - | - | - | - | Novel | |
CIC00535 | Ad |
PROM1
| NM_006017.2 | Het | 10 | c.1117C>T | p.(R373C) | + | Not | Pd | D | Dc | (rs137853006) [3] | |
CIC01196 | simplex |
PROM1
| NM_006017.2 | Ho | 12 | c.1354dup | p.(Y452Lfs*13) | + | - | - | - | - | [71] | |
CIC07045 | simplex |
PROM1
| NM_006017.2 | Ho | IVS 17 | c.1984-1G>T | r.(spl?) | Np | Highly | - | - | - | Novel (rs373680665) | |
CIC06642c
| Ad |
PROM1
| NM_006017.2 | Het | 1 | c.7dup | p.(L3Pfs*28) | + | - | - | - | - | Novel | |
CIC06698c
| Ad |
PROM1
| NM_006017.2 | Het | 1 | c.7dup | p.(L3Pfs*28) | + | - | - | - | - | Novel | |
CIC04945 | simplex |
PROM1
| NM_006017.2 | Het | 23 | c.2383T>C | p.(W795R) | + | Highly | Prd | D | Dc | Novel | |
PROM1
| NM_006017.2 | Het | IVS 13 | c.1579-1G>C | r.(spl?) | + | Highly | - | - | - | Novel | |||
CIC04965 | Ad |
CRX
| NM_000554.4 | Het | 4 | c.608_609del | p.(S203Ffs*32) | + | - | - | - | - | Novel | |
CIC3750 | simplex |
CRX
| NM_000554.4 | Het | 3 | c.121C>T | p.(R41W) | + | Highly | Prd | D | Dc | (rs104894672) [70] | |
CIC06321 | simplex | + |
RPGRIP1
| NM_020366.3 | Ho | 14 | c.2021C>A | p.(P674H) | + | Highly | Prd | T | Dc | Novel |
CIC00190 | simplex |
AIPL1
| NM_014336.4 | Het | 5 | c.769C>T | p.(L257F) | + | Moderately | Prd | D | Dc | Novel | |
AIPL1
| NM_014336.4 | Het | 5 | c.767T>G | p.(I256S) | + | Moderately | B | D | Dc | Novel | |||
Lower confidence
d
| ||||||||||||||
CIC00162 | Ar |
ABCA4
| NM_000350.2 | Het | 31 | c.4546_4547del | p.(Q1516Afs*38) | + | - | - | - | - | Novel | |
ABCA4
| NM_000350.2 | Het | 16 | c.2463G>A | p.(W821*) | + | - | - | - | - | Novel | |||
CIC05987 | Ar |
ABC4A
| NM_000350.2 | Het | 22 | c.3295T>C | p.(S1099P) | + | Highly | Pd | D | Dc | (rs61750119) [87] | |
ABC4A
| NM_000350.2 | Het | 22 | c.3322C>T | p.(R1108C) | Np | - | - | - | - | [88] | |||
CIC06694 | simplex |
ABC4A
| NM_000350.2 | Het | IVS36 | c.5196+1G>A | r.(spl?) | Np | - | - | - | - | [62] | |
ABC4A
| NM_000350.2 | Het | 22 | c.3322C>T | p.(R1108C) | Np | - | - | - | - | [86] | |||
CIC02712 | simplex | + |
PDE6C
| NM_006204.3 | Het | 10 | c.1325T>A | p.(M442K) | Np | Moderately | Pd | D | Dc | Novel |
PDE6C
| NM_006204.3 | Het | 10 | c.1375C>G | p.(Q459E) | Weakly | B | T | Dc | Novel | ||||
CIC00597 | simplex |
GUCY2D
| NM_000180.3 | Het | 14 | c.2747T>C | p.(I916T) | + | Moderately | Prd | D | Dc | [89] | |
CIC06352 | simplex |
GUCA1A
| NM_000409.3 | Het | 3 | c.149C>T | p.(P50L) | Np | Moderately | B | T | Dc | (rs104893968) [90] | |
CIC07188 | simplex |
PROM1
| NM_006017.2 | Het | 12 | c.1354dup | p.(Y452Lfs*13) | Np | - | - | - | - | [71] | |
PROM1
| NM_006017.2 | Het | IVS 12 | c.1454+2>C | r.(spl?) | Np | Highly | - | - | - | Novel | |||
CIC03241 | simplex |
CRX
| NM_000554.4 | Het | 4 | c.564dup | p.(A189Rfs*47) | + | - | - | - | - | Not clear if same mutation as in [69] | |
CIC07569 | simplex |
CRX
| NM_000554.4 | Het | IVS 3 | c.252+1G>A | r.(spl?) | Np | Highly | - | - | - | Novel |
ID | Type | Consang. | Gene | NM | Allele State | Exon | cDNA | Protein | Coseg. | Conservation | Polyphen2 | Sift | Mutation Taster | References |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
High confidence
| ||||||||||||||
CIC01571 | Ar |
C2Orf71
| NM_001029883.2 | Ho | 1 | c.2950C>T | p.(R984*) | + | - | - | - | - | [36] (RP) | |
CIC00643 | Ar | + |
C2Orf71
| NM_001029883.2 | Ho | 1 | c.1949G>A | p.(W650*) | Np | - | - | - | - | Novel (rs371289954) |
CIC03112 | Ar | + |
MERTK
| NM_006343.2 | Ho | 17 | c.2214del | p.(C738Wfs*32) | Np | - | - | - | - | [37] (RP) |
CIC01242 | Ar |
MERTK
| NM_006343.2 | Ho | 3_19 | c.483-?_c.3000+?del | - | + | - | - | - | - | Novel | |
CIC06514 | Ar | + |
RLBP1
| NM_000326.4 | Ho | 7_9 | c.526-?_c.954+?del | - | Np | - | - | - | - | Novel |
CIC03953 | simplex |
EYS
| NM_001292009.1 | Het | 11 | c.1673G>A | p.(W558*) | + | - | - | - | - | [23] (RP) (rs201823777) | |
EYS
| NM_001292009.1 | Het | 14 | c.2234A>G | p.(N745S) | + | Not | B | - | Poly | [23] (RP) (rs201652272) | |||
CIC05012 | simplex |
NMNAT1
| NM_022787.3 | Het | 5 | c.619C>T | p.(R207W) | Np | Weakly | B | D | Dc | [41] (LCA) (rs142968179) | |
NMNAT1
| NM_022787.3 | Het | 5 | c.769G>A | p.(E257K) | Np | Moderately | B | T | Dc | [42] (LCA) (rs150726175) | |||
CIC06499 | simplex |
NMNAT1
| NM_022787.3 | Het | 5 | c.619C>T | p.(R207W) | + | Weakly | B | D | Dc | [41] (LCA) (rs142968179) | |
NMNAT1
| NM_022787.3 | Het | 5 | c.769G>A | p.(E257K) | + | Moderately | B | T | Dc | [42] (LCA) (rs150726175) | |||
CIC05394 | Ar | + |
RDH12
| NM_152443.2 | Ho | 8 | c.806_810del | p.(A269Gfs*2) | Np | - | - | - | - | [43] (LCA) (rs386834261) |
CIC07241 | Ar | + |
RDH12
| NM_152443.2 | Ho | 7 | c.464C>T | p.(T155I) | Np | Highly | Pr | D | Dc | [44] (LCA) (rs121434337) |
CIC07447 | Ar |
RDH12
| NM_152443.2 | Het | 8 | c.806_810del | p.(A269Gfs*2) | + | - | - | - | [43] (LCA) (rs386834261) | ||
RDH12
| NM_152443.2 | Het | 8 | c.403A>G | p.(K135E) | + | Highly | Prd | T | Dc | Novel | |||
CIC00953 | simplex |
IQCB1
| NM_001023570.2 | Het | 6 | c.424_425del | p.(F142Pfs*5) | + | - | - | - | - | [49] (Senior-Loken/LCA) | |
IQCB1
| NM_001023570.2 | Het | 8 | c.686del | p.(T229Mfs*8) | + | - | - | - | - | Novel | |||
CIC01300 | Ar | + |
RP1
| NM_006269.1 | Ho | 4 | c.1719_1723del | p.(S574Cfs*7) | Np | - | - | - | - | [45] (arRP) |
CIC05272 | Ad |
BEST1
| NM_001139443.1 | Het | 4 | c.76G>A | p.(V26M) | + | Highly | Prd | D | Dc | [50] (ADVIRC) (rs121918289) | |
CIC01380 | Ar | + |
CRB1
| NM_201253.2 | Ho | 11 | c.3994T>G | p.(C1332G) | + | Highly | Prd | D | Dc | Novel (LCA) |
CIC00963 | Ar |
+
|
TULP1
| NM_003322.4 | Ho | 11 | c.1087G>A | p.(G363R) | + | Highly | Pd | D | Dc | Novel (LCA and arRP) |
Lower confidence
| ||||||||||||||
CIC05007 | Ad |
ROM1
| NM_000327.3 | Het | 1 | c.339del | p.(L114Sfs*8) | + | - | - | - | - | Novel (adRP) | |
Most likely not pathogenic
| ||||||||||||||
CIC05379 | simplex |
FSCN2
| NM_001077182.2 | Het | 1 | c.574C>T | p.(R192C) | + | Highly | Prd | D | Dc | Novel (adRP and adMD but questionable) (rs377025075) | |
CIC05604 | simplex |
FSCN2
| NM_001077182.2 | Het | 1 | Partial deletion | - | Np | - | - | - | - | Novel (adRP and adMD but questionable) |