. 2010 Oct;31(10):E1709–E1766. doi: 10.1002/humu.21336

Table 1.

Mutations identified in 80 unrelated patients with LCA/EORD, using LCA chip analysis and direct sequencing of CEP290, CRB1, RPE65, AIPL1, GUCY2D and CRX

				Allele 1				Allele 2		Reference

Patient	Origin	Par cons	Segr	Intron/exon	Nucleotide change	Amino acid change	Intron/exon	Nucleotide change	Amino acid change
CEP290

LCA-1	Belgium	-	X	I26	c.2991+1655A>G^*	p.Cys998X^*	I26	c.2991+1655A>G^*	p.Cys998X^*	(den Hollander et al., 2006)

LCA-2	Belgium	-	X	I26	c.2991+1655A>G	p.Cys998X	I26	c.2991+1655A>G	p.Cys998X	(den Hollander et al., 2006)

LCA-3⁺	Belgium	-	X	I26	c.2991+1655A>G^*	p.Cys998X^*	E6	c.322C>T	p.Arg108X	(den Hollander et al., 2006)

LCA-4	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	E25	c.2695C>T	p.Gln899X	(den Hollander et al., 2006)

LCA-5	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	E34	c.4393C>T	p.Arg1465X	(den Hollander et al., 2006), (Brancati et al., 2007) (CORS)

LCA-6	Belgium	-	X	I26	c.2991+1655A>G	p.Cys998X	E36	c.4723A>T	p.Lys1575X	(den Hollander et al., 2006), (Brancati et al., 2007; Perrault et al., 2007)

LCA-7^F	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	E36	c.4723A>T	p.Lys1575X	(den Hollander et al., 2006), (Brancati et al., 2007; Perrault et al., 2007)

LCA-8	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	E36	c.4723A>T	p.Lys1575X	(den Hollander et al., 2006), (Brancati et al., 2007; Perrault et al., 2007)

LCA-9	Belgium	-	X	I26	c.2991+1655A>G	p.Cys998X	E39	c.5344C>T	p.Arg1782X	(den Hollander et al., 2006)

LCA-10	Lithuania	-	X	I26	c.2991+1655A>G	p.Cys998X	E6	c.384 385del	p.Asp128GlufsX17	(den Hollander et al., 2006)

LCA-11	Belgium	-	X	I26	c.2991+1655A>G	p.Cys998X	E6	c.437del	p.Glu146GlyfsX17	(den Hollander et al., 2006)

LCA-12	The Netherlands	-	NA	126	c.2991+1655A>G^*	p.Cys998X^*	E19	c.1859_1862del	p.Arg621IlefsX2	(den Hollander et al., 2006), (Perrault et al., 2007)

LCA-13	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	E29	c.3422dup	p.Leu1141PhefsX5	(den Hollander et al., 2006)

LCA-14	Belgium/Morocco	-	X	I26	c.2991+1655A>G^*	p.Cys998X^*	E31	c.4001del	p.Thr1334IlefsX2	(den Hollander et al., 2006)

LCA-15 (Perrault et al., 2007)	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	E37	c.4962_4963del	p.Glu1656AsnfsX3	(den Hollander et al., 2006), (Perrault et al., 2007)

LCA-16⁺	Belgium/Greece	-	X	I26	c.2991+1655A>G	p.Cys998X	E40	c.5493del	p.Ala1832ProfsX19	(den Hollander et al., 2006), (Brancati et al., 2007; Frank et al., 2008) (CORS)

LCA-17	Belgium	-	X	I26	c.2991+1655A>G	p.Cys998X	E40	c.5519 5537del	p.Lys1840ArgfsX5	(den Hollander et al., 2006)

LCA-18	Belgium	-	X	I26	c.2991+1655A>G	p.Cys998X	E43	c.5865 5867delins GG	p.Glu1956GlyfsX9	(den Hollander et al., 2006)

LCA-19	Belgium	-	X	I26	c.2991+1655A>G	p.Cys998X	I13	c.1189+1G>A	Splice defect	(den Hollander et al., 2006)

LCA-20⁺ (Yzer et al., 2006)	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	121	c.2218-2A>C	Splice defect	(den Hollander et al., 2006)

LCA-21	Belgium	-	X	I26	c.2991+1655A>G	p.Cys998X	I28-E29	c.3310-1 3310delinsAA	Splice defect	(den Hollander et al., 2006)

LCA-22	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	I28-E29	c.3310-1 3310delinsAA	Splice defect	(den Hollander et al., 2006)

LCA-23	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	I28-E29	c.3310-1 3310delinsAA	Splice defect	(den Hollander et al., 2006)

LCA-24	Belgium	-	NA	E36	c.4723A>T	p.Lys1575X	E36	c.4723A>T	p.Lys1575X	(Perrault et al., 2007)

LCA-25^F	Belgium	-	X	E36	c.4723A>T	p.Lys1575X	E35	c.4696G>C	p.Ala1566Pro UV	(Perrault et al., 2007)

LCA-26	Belgium		X	E18	c.1824G>A	p.=, splice site	E38	c.5081T>C	p.Leu1694Pro UV

LCA-27	Belgium	-	NA	I26	c.2991+1655A>G	p.Cys998X	?	?	?	(den Hollander et al., 2006)

SLS-1	Pakistan	FC	X	E2	c.21G>T	p.Trp7Cys	E2	c.21G>T	p.Trp7Cys	(Valente et al., 2006b) (CORS)

SLS-2	Belgium	-	NA	E36	c.4723A>T	p.Lys1575X	E34	c.4393C>T	p.Arg1465X	(Perrault et al., 2007), (Brancati et al., 2007) (CORS)

SLS-3	Belgium	-	NA	E36	c.4723A>T	p.Lys1575X	E34	c.4393C>T	p.Arg1465X	(Perrault et al., 2007), (Brancati et al., 2007) (CORS)

CORS-1⁺ (Brancati et al., 2007)	Belgium	SD	NA	E36	c.4723A>T	p.Lys1575X	E34	c.4393C>T	p.Arg1465X	(Perrault et al., 2007), (Brancati et al., 2007) (CORS)

LCA-JS-1	Belgium	-	X	I40	c.5587-1G>C	Splice defect	E31	c.3793C>T	p.Gln1265X	(Perrault 2007), (Baala et al., 2007) (ML)

LCA-JS-2 II-1				E54	c.7366 7369del	p.Thr2457AlafsX27	E54	c.7366 7369del	p.Thr2457AlafsX27

LCA-JS-2 II-2	ND	+	X	E54	c.7366 7369del	p.Thr2457AlafsX27	E54	c.7366 7369del	p.Thr2457AlafsX27

LCA-JS-3	Belgium	-	NA	I28-E29	c.3310-1 3310delinsAA	Splice defect	E54	c.7341dup	p.Leu2448ThrfsX8	(Sayer et al., 2006)

CRB1

LCA-28	Belgium	-	NA	E7	c.2401A>T^*	p.Lys801X^*	E7	c.2401A>T^*	p.Lys801X^*	(den Hollander et al., 2001)

LCA-29 (Yzer et al., 2006)	Belgium	-	NA	E7	c.2401A>T^*	p.Lys801X^*	E5	c.1084C>T	p.Gln362X	(den Hollander et al., 2001), (Yzer et al., 2006)

LCA-30	Belgium	-	X	E7	c.2401A>T^*	p.Lys801X^*	E7	c.2290C>T^*	p.Arg764Cys^*	(den Hollander et al., 2001), (Lotery et al., 2001)

LCA-31 (Yzer et al., 2006)	Belgium	-	X	E7	c.2401A>T^*	p.Lys801X^*	E8	c.2688T>A^*	p.Cys896X^*	(den Hollander et al., 2001), (Hanein et al., 2004)

LCA-32 (Yzer et al., 2006)	Belgium	-	NA	E7	c.2401A>T^*	p.Lys801X^*	E8	c.2688T>A^*	p.Cys896X^*	(den Hollander et al., 2001), (Hanein et al., 2004)

LCA-33	Belgium	-	NA	E7	c.2401A>T^*	p.Lys801X^*	E9	c.2843G>A^*	p.Cys948Tyr^*	(den Hollander et al., 2001), (Lotery et al., 2001)

LCA-34	Belgium	-	X	E7	c.2401A>T^*	p.Lys801X^*	I11	c.4006-1G>T	Splice defect	(den Hollander et al., 2001)

LCA-35	Belgium	+	NA	E9	c.2843G>A^*	p.Cys948Tyr^*	E9	c.2843G>A^*	p.Cys948Tyr^*	(Lotery et al., 2001)

LCA-36	ND	-	NA	E9	c.2843G>A^*	p.Cys948Tyr^*	Ell	c.3988G>T^*	p.Glu1330X^*	(Lotery et al., 2001), (LCA chip)

LCA-37	Belgium	-	X	E9	c.2843G>A^*	p.Cys948Tyr^*	I8	c.2842+5G>A^*	Splice defect^*	(Lotery et al., 2001), (den Hollander et al., 1999)

LCA-38	Belgium	-	X	E9	c.2843G>A^*	p.Cys948Tyr^*	I8	c.2842+5G>A^*	Splice defect^*	(Lotery et al., 2001), (den Hollander et al., 1999)

LCA-39a				E9	c.2843G>A^*	p.Cys948Tyr^*	I8	c.2842+5G+A^*	Splice defect^*	(Lotery et al., 2001), (den Hollander et al., 1999)

LCA-39b	Belgium	-	X	I11	c.4005+1G>A	Splice defect	I8	c.2842+5G>A	Splice defect	(Hanein et al., 2004), (den Hollander et al., 1999)

LCA-40	Belgium	-	NA	I11	c.4005+1G>A^*	Splice defect^*	I8	c.2842+5G>A^*	Splice defect^*	(Hanein et al., 2004), (den Hollander et al., 1999)

LCA-41 II-1				E7	c.2441 2442del	p.Leu814ArgfsX23	E9	c.3713 3716dup	p.Cys1240ProfsX24

LCA-41 II-2				E7	c.2441 2442del	p.Leu814ArgfsX23	E9	c.3713 3716dup	p.Cys1240ProfsX24

LCA-42	ND	+	NA	E11	c.3879G>A^*	p.Trp1293X^*	E11	c.3879G>A^*	p.Trp1293X^*	(Hanein et al., 2004)

EORD-1 II-1				E9	c.2843G>A^*	p.Cys948Tyr^*	E7	c.2401A>T^*	p.Lys801X^*	(Lotery et al., 2001), (den Hollander et al., 2001)

EORD-1 II-2	Belgium	-	X	E9	c.2843G>A	p.Cys948Tyr	E7	c.2401A>T	p.Lys801X	(Lotery et al., 2001), (den Hollander et al., 2001)

EORD-2	Belgium		NA	E9	c.2843G>A	p.Cys948Tyr	E4	c.929G>A	p.Cys310Tyr	(Lotery et al., 2001)

EORD-3	Belgium	-	X	E9	c.2843G>A^*	p.Cys948Tyr^*	E6	c.1472A>T	p.Asp491Val UV	(Lotery et al., 2001)

EORD-4	Belgium		NA	E5	c.1084C>T^*	p.Gln362X^*	E5	c.1084C>T^*	p.Gln362X^*	(Yzer et al., 2006)

EORD-5	Belgium	-	NA	E7	c.2290C>T^*	p.Arg764Cys^*	E7	c.2290C>T^*	p.Arg764Cys^*	(Lotery et al., 2001)

RPE65

LCA-43	Turkey	FC	X	E3	c.131G>A^*	p.Arg44Gln^*	E3	c.131G>A^*	p.Arg44Gln^*	(Simovich et al., 2001)

LCA-44	Turkey	FC	X	E6	c.542C>T	p.Pro181Leu	E6	c.542C>T	p.Pro181Leu

LCA-45a				E7	c.700C>T^*	p.Arg234X^*	E9	c.991 993dup	p.Trp331dup	(Marlhens et al., 1997)

LCA-45b				E9	c.991 993dup	p.Trp331dup	E9	c.991 993dup	p.Trp331dup

LCA-46	Portugal		X (c.10 22T> C)	E10	c.1022T>C^*	p.Leu341Ser^*	E5	c.361delT	p.Ser121LeufsX6 de novo	(Morimura et al., 1998) (ARRP)

LCA-47	Belgium	-	X	E14	c.1590del^*	p.Phe530LeufsX40^*	E14	c.1590del^*	p.Phe530LeufsX40^*	(Yzer et al., 2006)

LCA-48	Belgium	-	X	E14	c.1590del	p.Phe530LeufsX40	E5	c.370C>T^*	p.Arg124X^*	(Yzer et al., 2006), (Morimura et al., 1998)

LCA-49	Belgium	-	X	E14	c.1590del^*	p.Phe530LeufsX40^*	11	c.11+5G>A^*	Splice defect^*	(Yzer et al., 2006), (Gu et al., 1997)

LCA-50	Belgium/Russia (mother)	-	X	E9	c.886dupA	p.Arg296LysfsX7	11	c.11+5G>A^*	Splice defect^*	(Gu et al., 1997)

GUCY2D

LCA-51	Morocco/Belgium	-	NA	E2	c.389del	p.Pro130LeufsX36	I13	c.2577-2A>C	Splice defect	(Perrault et al., 1996)

LCA-52	Turkey	TC	NA	E8	c.1694T>C^*	p.Phe565Ser^*	E8	c.1694T>C^*	p.Phe565Ser^*	(Perrault et al., 1996)

LCA-53	Belgium		NA	E12	c.2302C>T^*	p.Arg768Trp^*	E12	c.2302C>T^*	p.Arg768Trp^*	(Lotery et al., 2000)

LCA-54	Morocco/Belgium	-	X	E12	c.2302C>T^*	p.Arg768Trp^*	E8	c.1694T>C^*	p.Phe565Ser^*	(Lotery et al., 2000), (Perrault et al., 1996)

LCA-55	Belgium	-	X	E12	c.2302C>T^*	p.Arg768Trp^*	E14	c.2598G>C	p.Lys866Asn	(Lotery et al., 2000)

LCA-56	Belgium/France	-	X	E2	c.587A>T	p.Glu196Val UV	Ell	c.2132C>T	p.Pro711Leu UV

LCA-57	Africa	-	NA	E8	c.1724C>T^*	p.Pro575Leu^* UV	?	?	?	(Koenekoop et al., 2002)

AIPL1

LCA-58 (Yzer et al., 2006)	Belgium	-	X	E6	c.834G>A^*	p.Trp278X^*	E6	c.834G>A	p.Trp278X	(Sohocki et al., 2000a)

LCA-59	Belgium	-	NA	E6	c.834G>A^*	p.Trp278X^*	E6	c.834G>A^*	p.Trp278X^*	(Sohocki et al., 2000a)

LCA-60	Belgium		NA	E6	c.834G>A^*	p.Trp278X^*	E6	c.834G>A^*	p.Trp278X^*	(Sohocki et al., 2000a)

LCA-61	Belgium	-	X	E6	c.834G>A^*	p.Trp278X^*	E6	c.834G>A^*	p.Trp278X^*	(Sohocki et al., 2000a)

LCA-62	Africa	-	in cis	E3	c.341C>T^*	p.Thr114Ile^*UV	?	?	?	(Sohocki et al., 2000b)
				c.1126C>T	p.Pro376SerUV

CRX

LCA-63	Belgium	SC	NA	E4	c.425A>G^*	p.Tyr142Cys^* UV	?	?	?	(Vallespin et al., 2007a)

LCA-64	Ruanda		NA	E3	c.724G>A^*	p.Val242Met^* UV	?	?	?	(Swain et al., 1997)

RDH12

EORD-6	Belgium	-	X	E6	c.806_810del^*	p.Ala269GlyfsX2^*	E8	c.698T>A	p.Val233Asp	(Janecke et al., 2004), https://www.carverlab.org/carver-mutation-database

EORD-7	Belgium	+	X	E6	c.806_810del^*	p.Ala269GlyfsX2^*	E7	c.524C>T	p.Ser175Leu	(Janecke et al., 2004)

EORD-8	Belgium			E6	c.806_810del	p.Ala269GlyfsX2	E6	c.806_810del	p.Ala269GlyfsX2	(Janecke et al., 2004)

RPGRIP1

LCA-65	Belgium			E16	c.2668C>T^*	p.Arg890X^*	?	?	?	(Gerber et al., 2001)

Novel mutations are indicated in bold.

⁺

patients carrying a heterozygous mutation in an additional gene: LCA-3 (AHI1, c.2273A>C, p.His758Pro), LCA-16 (RPE65, c.253C>T, p.Arg85Cys) (Stone, 2007), LCA-20 (CRB1, c.2401A>T, p.Lys801X) (den Hollander et al., 2001) and CORS-1 (AHI1, c.2433T>G, p.Asn81 1Lys).

identified through LCA chip analysis.

LCA-7 and LCA-25 are distantly related. X: segregation analysis performed and segregation confirmed. NA: no material available of family members. Reference: first publication describing the mutation in patients with LCA or EORD. In case of CEP290, these references may also refer to papers dealing with other phenotypes (phenotype mentioned between brackets). Seven patients were already described (corresponding reference is indicated in the first column).

Abbreviations used: par cons: parental consanguinity; segr: segregation; FC: first cousins; SC: second cousins; TC: third cousins; SD: second degree; ND: no data; UV, unclassified variant; LCA, Leber Congenital Amaurosis; SLS, Senior-Loken syndrome; JS, joubert syndrome; ARRP, autosomal recessive retinitis pigmentosa; CORS, cerebello-oculo-renal syndrome; ML, Meckel-like syndrome.