c.2991+1655A>G (p.Cys998X; wild-type)
Variant ID Exon OMIM ID
15 Intron 26
Domains RNA effect EPP Control frequency Controls origin NetGene2 BDGP
SMC,  CC V splicing change 3 0/223 - 1/248 (heterozygous) - 0/50 French Canadian - Dutch - Spanish
The reading frame is interrupted by a premature STOP codon.
The mRNA produced might be targeted for nonsense mediated decay (NMD).

This mutation creates a strong splice-donor site that results in the introduction of a cryptic exon between exons 26 and 27, thereby leading to a premature stopcodon immediately downstream of exon 26 (p.Cys998X). Interestingly, approximately 50% of wild-type product is still present (den Hollander et al.).

McEwen and colleagues investigated olfactory function in the French‚ÄěCanadian LCA family which originally revealed this mutation. All LCA patients examined exhibited severely abnormal olfactory function, whereas heterozygous carriers exhibited mild to severe microsmia. Further research in the rd16 mouse suggested that CEP290 might be a key mediator involved in G-protein trafficking in dendritic knobs of the olfactory sensory neurons (McEwen et al.).

So far, this mutation is found exclusively in patients with isolated LCA. It is the most recurrent mutation in LCA in the North-Western of Europe, with a contribution of up to 20% of all LCA cases (den Hollander et al., Perrault et al.). In the South of Europe, Korea and Saudi-Arabia, however, this mutation seems to have a significantly lower prevalence (Simonelli et al., Vallespin et al., Seong et al., Li et al.).

  CEP290 Additional gene 1
Patient information Allele 1 Allele 2   Allele 1 Allele 2
Patient ID Family ID Gender Age Origin Disease Segregation Parental consanguinity Consanguinity degree Exon/intron Nucleotide nomencl. Protein nomencl. Detection method Exon/intron Nucleotide nomencl. Protein nomencl. Detection method Reference Gene Nucleotide nomencl. Protein nomencl. Detection method Nucleotide nomencl. Protein nomencl. Detection method
French-Canadian family IV-6 French-Canadian family male Canada LCA yes yes first cousins Intron 26 c.2991+1655A>G p.Cys998X mRNA screening Intron 26 c.2991+1655A>G p.Cys998X mRNA screening              
French-Canadian family IV-7 French-Canadian family male Canada LCA yes yes first cousins Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger)              
French-Canadian family IV-8 French-Canadian family male Canada LCA yes yes first cousins Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger)              
French-Canadian family IV-9 French-Canadian family female Canada LCA yes yes first cousins Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger)              
12832 12832   Netherlands LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR              
13168 13168   Germany LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 22 c.2249T>G p.Leu750X Direct sequencing (Sanger)              
14964 14964   Germany LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 54 - CDS c.7341dupA p.Leu2448ThrfsX7 Direct sequencing (Sanger)              
15103 15103   Germany LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 21 c.2118_2122dupTCAGC p.Thr709SerfsX8 Direct sequencing (Sanger)              
15212 15212 male Germany LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 43 c.5866G>T p.Glu1956X Direct sequencing (Sanger)              
16317 16317 female Netherlands LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR              
17971 17971 female Netherlands LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 31 c.3814C>T p.Arg1272X Direct sequencing (Sanger)              
20152 20152   Netherlands LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 10 c.679_680delGA p.Glu227SerfsX1 Direct sequencing (Sanger)              
21365 21365 male Netherlands LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR              
21393 21393 female Netherlands LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 5 c.265dupA p.Thr89AsnfsX1 Direct sequencing (Sanger)              
21918 21918 male Netherlands LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Intron 3 c.180+1G>T splice defect Direct sequencing (Sanger)              
27228 27228   Canada LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR              
27242 27242 female Canada LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 16 c.1550delT p.Leu517X Direct sequencing (Sanger)              
27245 27245 male Canada LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 32 c.4115_4116delTA p.Ile1372LysfsX4 Direct sequencing (Sanger)              
27246 27246 male Canada LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 37 c.4966G>T p.Glu1656X Direct sequencing (Sanger)              
27250 27250   Italy LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Allele-specific PCR Exon 42 c.5813_5817delCTTTA p.Thr1938AsnfsX15 Direct sequencing (Sanger)              
818   10 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Intron 26 c.2991+1655A>G p.Cys998X DHPLC              
821   4 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Intron 26 c.2991+1655A>G p.Cys998X DHPLC              
831   1 y 6 m France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Intron 26 c.2991+1655A>G p.Cys998X DHPLC              
850   1 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Intron 26 c.2991+1655A>G p.Cys998X DHPLC              
695   28 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Intron 40 c.5587-1G>C ? DHPLC              
290   15 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Intron 40 c.5587-1G>C ? DHPLC              
654   4 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Exon 19 c.1855-1858delAAAG p.Lys619LysfsX3 DHPLC              
726   3 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Exon 28 c.3175insA p.Ile1059AsnfsX10 DHPLC              
798   11 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Intron 38 c.5226+1G>A ? DHPLC              
13011   5 m Switzerland LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Exon 38 c.5163delT p.The1721fsX2 DHPLC              
13045   11 m Switzerland LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Exon 38 c.5163delT p.The1721fsX2 DHPLC              
13108   3 m Switzerland LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Exon 38 c.5163delT p.The1721fsX2 DHPLC              
659   4 y Sweden LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Exon 20 c.1992delT p.Asp664AspfsX10 DHPLC              
552   1 y 1 m Italy LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X DHPLC Exon 14 c.1219_1220delAT p.Met407GlufsX13 DHPLC              
D582   5 y Greece LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger)              
105 11 yrs 105   11 y France LCA yes unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 32 c.5255-5256delGG p.Arg1752ArgfsX7 Direct sequencing (Sanger)              
105 1 yrs 105   1 y France LCA yes unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 32 c.5255-5256delGG p.Arg1752ArgfsX7 Direct sequencing (Sanger)              
166 (1) 166   France LCA yes unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 48 c.6604del p.Ile2202LeufsX24 Direct sequencing (Sanger)              
166 (2) 166   France LCA yes unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 48 c.6604del p.Ile2202LeufsX24 Direct sequencing (Sanger)              
166 (3) 166   France LCA yes unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 48 c.6604del p.Ile2202LeufsX24 Direct sequencing (Sanger)              
166 (4) 166   France LCA yes unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 48 c.6604del p.Ile2202LeufsX24 Direct sequencing (Sanger)              
166 (5) 166   France LCA yes unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 48 c.6604del p.Ile2202LeufsX24 Direct sequencing (Sanger)              
196   1 y 6 m France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger)              
247   2 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 37 c.4882C>T p.Gln1628X Direct sequencing (Sanger)              
264   25 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 31 c.3922C>T p.Gln1308X Direct sequencing (Sanger)              
317   9 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger)              
334   9 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 42 c.5850delT p.Phe1950LeufsX14 Direct sequencing (Sanger)              
355   1 y 6 m France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 19 c.1910-2A>G Splice Direct sequencing (Sanger)              
382   10 y Italy LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 28 c.3292G>T p.Glu1098X Direct sequencing (Sanger)              
389   Belgium LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 37 c.4962_4963delAA p.Gln1654GlnfsX4 Direct sequencing (Sanger)              
420   2 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger)              
445   3 y France LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 31 c.4028delA p.Lys1343ArgfsX1 Direct sequencing (Sanger)              
513   5 m United Kingdom LCA unknown unknown Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 6 c.384-387delTAGA p.Asp128GlufsX33 Direct sequencing (Sanger)              
P1 male 7 y LCA unknown unknown Intron 26 c.2991+1655A>G Splice defect              
P2 female 11 y LCA unknown unknown Intron 26 c.2991+1655A>G Splice defect Intron 26 c.2991+1655A>G Splice defect              
P3 male 14 y LCA unknown unknown Intron 26 c.2991+1655A>G Splice defect c.4882C>T p.Q1628X              
P4 sibs male 17 y LCA unknown unknown Intron 26 c.2991+1655A>G Splice defect Exon 41 c.5668G>T p.G1890X              
P5 sibs female 19 y LCA unknown unknown Intron 26 c.2991+1655A>G Splice defect Exon 41 c.5668G>T p.G1890X              
P6 female 20 y LCA unknown unknown Intron 26 c.2991+1655A>G Splice defect Intron 26 c.2991+1655A>G Splice defect              
P7 male 26 y LCA unknown unknown Intron 26 c.2991+1655A>G Splice defect Exon 14 c.1260_1264delTAAAG p.T420fs              
P8 male 48 y LCA unknown unknown Intron 26 c.2991+1655A>G Splice defect              
A1   Italy LCA yes unknown Intron 26 c.2991+1655A>G p.C998X DHPLC c.1219–1220delAT p.H406fsX420 DHPLC              
A4   Italy LCA yes unknown Intron 26 c.2991+1655A>G p.C998X DHPLC c.566C>G p.S189X DHPLC              
A141   Italy LCA yes unknown Intron 26 c.2991+1655A>G p.C998X DHPLC Exon 38 c.5041–5046delA p.V1680FSX1683 DHPLC              
A12   Italy LCA yes unknown c.2991+1655A>G p.C998X DHPLC c.3292G>T p.E1098X DHPLC              
A   Spain LCA unknown unknown c.2991_1655A>G Direct sequencing (Sanger) c.2991_1655A>G Direct sequencing (Sanger)              
B   Spain LCA unknown unknown c.2991_1655A>G Direct sequencing (Sanger) c.2991_1655A>G Direct sequencing (Sanger)              
C   Spain LCA unknown unknown c.2991_1655A>G Direct sequencing (Sanger)              
D   Spain LCA unknown unknown c.2991_1655A>G Direct sequencing (Sanger)              
LCA-1 LCA-1 male 3 y 5 m Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Asper Ophthalmics LCA chip Intron 26 c.2991+1655A>G p.Cys998X Asper Ophthalmics LCA chip                
LCA-2 LCA-2 male Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger)                
LCA-3 LCA-3 male Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Asper Ophthalmics LCA chip Exon 6 c.322C>T p.Arg108X Direct sequencing (Sanger)   NM_001134831 c.2273A>C p.His758Pro Direct sequencing (Sanger)
LCA-4 LCA-4 female Belgium LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 25 c.2695C>T p.Gln899X Direct sequencing (Sanger)                
LCA-5 LCA-5 male Belgium LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 34 c.4393C>T p.Arg1465X Direct sequencing (Sanger)                
LCA-6 LCA-6 female Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 36 c.4723A>T p.Lys1575X Direct sequencing (Sanger)                
LCA-7 LCA-7 male Belgium LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 36 c.4723A>T p.Lys1575X Direct sequencing (Sanger)                
LCA-8 LCA-8 female Belgium LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 36 c.4723A>T p.Lys1575X Direct sequencing (Sanger)                
LCA-9 LCA-9 male Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 39 c.5344C>T p.Arg1782X Direct sequencing (Sanger)                
LCA-10 LCA-10 female Lithuania LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 6 c.384_385del p.Asp128GlufsX17 Direct sequencing (Sanger)                
LCA-11 LCA-11 male Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 6 c.437del p.Glu146GlyfsX17 Direct sequencing (Sanger)                
LCA-12 LCA-12 male Netherlands LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Asper Ophthalmics LCA chip Exon 19 c.1859_1862del p.Arg621IlefsX2 Direct sequencing (Sanger)                
LCA-13 LCA-13 female Belgium LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 29 c.3422dup p.Leu1141PhefsX5 Direct sequencing (Sanger)                
LCA-14 LCA-14 female Belgium; Morocco LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Asper Ophthalmics LCA chip Exon 31 c.4001del p.Thr1334IlefsX2 Direct sequencing (Sanger)                
LCA-16 LCA-16 male Belgium; Greece LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 40 c.5493del p.Ala1832ProfsX19 Direct sequencing (Sanger)                
LCA-17 LCA-17 male Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 40 c.5519_5537del p.Lys1840ArgfsX5 Direct sequencing (Sanger)                
LCA-18 LCA-18 male Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 43 c.5865_5867delinsGG p.Glu1956GlyfsX9 Direct sequencing (Sanger)                
LCA-19 LCA-19 male Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 13 c.1189+1G>A p.? Direct sequencing (Sanger)                
LCA-20 LCA-20 female Belgium LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 21 c.2218-2A>C p.? Direct sequencing (Sanger)                
LCA-23 LCA-23 female Belgium LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 28 c.3310-1_3310delinsAA p.? Direct sequencing (Sanger)                
LCA-22 LCA-22 male Belgium LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 28 c.3310-1_3310delinsAA p.? Direct sequencing (Sanger)                
LCA-21 LCA-21 male Belgium LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Intron 28 c.3310-1_3310delinsAA p.? Direct sequencing (Sanger)                
LCA-27 LCA-27 male Belgium LCA unknown no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger)                
18871 W02-004 male 12 y Netherlands LCA yes no Intron 26 c.2991+1655A>G p.Cys998X Direct sequencing (Sanger) Exon 7 c.451C>T p.Arg151X Direct sequencing (Sanger)