ABCMdb

PMID: 22229821

Duno M, Schwartz M, Larsen PL, Rosenberg T
Phenotypic and genetic spectrum of Danish patients with ABCA4-related retinopathy.
Ophthalmic Genet. 2012 Dec;33(4):225-31. doi: 10.3109/13816810.2011.643441. Epub 2012 Jan 9., [PubMed]

Sentences

No. Mutations Sentence Comment

48 ABCA4 p.Trp1551* Seven of the novel mutations were predicted to affect correct RNA maturation either by disrupting conserved splice sites (c.4668-2A>G, c.4773 + 3A>G, c.4773 + 5G>A, c.5584 + 1G>A, c.6386 + 1G>A), introducing a frame shift (c.2408delG) or by the introduction of a premature stop codon (c.4653G>A, p.W1551X). Login to comment 49 ABCA4 p.Trp1551* Seven of the novel mutations were predicted to affect correct RNA maturation either by disrupting conserved splice sites (c.4668-2A>G, c.4773ߙ+ߙ3A>G, c.4773ߙ+ߙ5G>A, c.5584ߙ+ߙ1G>A, c.6386ߙ+ߙ1G>A), introducing a frame shift (c.2408delG) or by the introduction of a premature stop codon (c.4653G>A, p.W1551X). Login to comment 53 ABCA4 p.Lys2160Glu The c.6478 A>G (p.K2160E) mutation affects the second last base in the exon 47, which is highly conserved, and the mutation might therefore affect the donor splice site rather than the protein structure. Login to comment 54 ABCA4 p.Lys2160Glu The c.6478 A>G (p.K2160E) mutation affects the second last base in the exon 47, which is highly conserved, and the mutation might therefore affect the donor splice site rather than the protein structure. Login to comment 56 ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Leu541Pro ABCA4 p.Cys1488Arg ABCA4 p.Cys1490Tyr ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Val767Asp ABCA4 p.Arg2030Gln ABCA4 p.Arg2030Gln ABCA4 p.Trp1551* ABCA4 p.Ala1357Thr ABCA4 p.Cys748Tyr ABCA4 p.Cys2150Tyr ABCA4 p.Phe608Leu ABCA4 p.Thr972Asn ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys ABCA4 p.Leu1246Val ABCA4 p.Gly550Arg ABCA4 p.Gly1127Glu ABCA4 p.Pro62Ser Table 1 Mutations identified by HRM in the initial 50 heterozygous patients Patient Mutation 1 (Asper) Mutation 2 (HRM) RefDNA Protein Exon/intron DNA Protein Exon/intron D043 c.2588G>C p.G863A 17 c.184 C>T p.P62S 3 New D069 c.3113C>T p.A1038V 21 c.1529 T>G p.L510R 11 New D050 c.2588G>C p.G863A 17 c.1529 T>G p.L510R 11 New D112 c.2894A>G p.N965S 19 c.1529 T>G p.L510R 11 New D099 c.6089G>A p.R2030Q 44 c.1529 T>G p.L510R 11 New D165 c.1822T>C p.F608L 13 c.2243 G>A p.C748Y 15 New D166 c.2588G>C p.G863A 17 c.2300 T>A p.V767D 15 Known D117 c.3191-2A>G na IVS21 c.2408delG na 16 New D135 c.2894A>G p.N965S 19 c.2408delG na 16 New D147 c.2894A>G p.N965S 19 c.2408delG na 16 New D173 c.4469G>A p.C1490Y 30 c.2915C>A p.T972N 19 Known D013* c.1622C>T p.L541P 12 c.1313C>T p.A1038V 21 Known D181 c.6089G>A p.R2030Q 44 c.3380 G>A p.G1127E 23 New D018 c.6449G>A p.C2150Y 47 c.3736 C>G p.L1246V 25 New D191 c.2588G>C p.G863A 17 c.4069 G>A p.A1357T 27 New D167 c.5461-10T>C na IVS38 c.4102 C>T p.R1368C 27 New D022 c.4462T>C p.C1488R 30 c.4102 C>T p.R1368C 27 New D108 c.1648G>A p.G550R 12 c.4102 C>T p.R1368C 27 New D414 c.2588G>C p.G863A 17 c.4653 G>A p.W1551X 32 New D027 c.2588G>C p.G863A 17 c.4668-2A>G na IVS32 New D136 c. Login to comment 57 ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Leu1580Ser ABCA4 p.Thr901Ala [1622C>T+3113C>T] p.[L541P+A1038V] 12 c.4739T>C p.L1580S 33 Known D444 c.2701A>G p.T901A 18 c.4773 + 3A>G na IVS33 New D034 c.2588G>C p.G863A 17 c.4773 + 5G>A na IVS33 New D178 c.3113C>T p.A1038V 21 c.5523_5528del p.1843_1844delRG 39 New D110 c. Login to comment 58 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Leu541Pro ABCA4 p.Cys1488Arg ABCA4 p.Cys1490Tyr ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Val767Asp ABCA4 p.Arg1108Cys ABCA4 p.Arg2030Gln ABCA4 p.Arg2030Gln ABCA4 p.Arg2030Gln ABCA4 p.Trp1551* ABCA4 p.Lys2160Glu ABCA4 p.Ala1357Thr ABCA4 p.Cys748Tyr ABCA4 p.Cys2150Tyr ABCA4 p.Phe608Leu ABCA4 p.Thr972Asn ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys ABCA4 p.Leu1246Val ABCA4 p.Gly550Arg ABCA4 p.Gly1127Glu ABCA4 p.Pro62Ser ABCA4 p.Leu2033Arg ABCA4 p.Arg1898His [1622C>T+3113C>T] p.[L541P+A1038V] 12 c.5584 + 1G>A na IVS39 New D188 c.5461-10T>C na IVS38 c.5693G>A p.R1898H 40 Known D433 c.5882G>A p.G1961E 42 c.6005 + 1G>A na IVS43 Known D134 c.4667 09;+ 2G>T na IVS32 c.6098 T>G p.L2033R 44 New D186 c.3322C>T p.R1108C 22 c.6386 +009;1G>A na IVS46 New D182 c.6089G>A p.R2030Q 44 c.6386 + 1G>A na IVS46 New D189 c.2894A>G p.N965S 19 c.6478 A>G p.K2160E 47 New *p.L541P and p.A1038V might be located on the same allele. Login to comment 59 ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Leu1580Ser ABCA4 p.Thr901Ala [1622C>T+3113C>T] p.[L541P+A1038V] 12 c.4739T>C p.L1580S 33 Known D444 c.2701A>G p.T901A 18 c.4773ߙ+ߙ3A>G na IVS33 New D034 c.2588G>C p.G863A 17 c.4773ߙ+ߙ5G>A na IVS33 New D178 c.3113C>T p.A1038V 21 c.5523_5528del p.1843_1844delRG 39 New D110 c. Login to comment 60 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Asn965Ser ABCA4 p.Arg1108Cys ABCA4 p.Arg2030Gln ABCA4 p.Lys2160Glu ABCA4 p.Leu2033Arg ABCA4 p.Arg1898His [1622C>T+3113C>T] p.[L541P+A1038V] 12 c.5584ߙ+ߙ1G>A na IVS39 New D188 c.5461-10T>C na IVS38 c.5693G>A p.R1898H 40 Known D433 c.5882G>A p.G1961E 42 c.6005ߙ+ߙ1G>A na IVS43 Known D134 c.4667ߙ+ߙ2G>T na IVS32 c.6098 T>G p.L2033R 44 New D186 c.3322C>T p.R1108C 22 c.6386ߙ+ߙ1G>A na IVS46 New D182 c.6089G>A p.R2030Q 44 c.6386ߙ+ߙ1G>A na IVS46 New D189 c.2894A>G p.N965S 19 c.6478 A>G p.K2160E 47 New *p.L541P and p.A1038V might be located on the same allele. Login to comment 61 ABCA4 p.Cys748Tyr ABCA4 p.Leu1246Val ABCA4 p.Pro62Ser PolyPhen2 predicted all substitutions except for c.3736C>G; p.L1246V to be damaging, whereas AlignGVGD assigned variable scores for all except p.P62S and p.C748Y which were given a "less likely" score. Login to comment 63 ABCA4 p.Cys748Tyr ABCA4 p.Leu1246Val ABCA4 p.Pro62Ser PolyPhen2 predicted all substitutions except for c.3736C>G; p.L1246V to be damaging, whereas AlignGVGD assigned variable scores for all except p.P62S and p.C748Y which were given a "less likely" score. Login to comment 66 ABCA4 p.Lys2160Glu ABCA4 p.Leu510Arg ABCA4 p.Gly1127Glu Three of the four recurrent mutations were identified (p.L510R, c.2408delG and c.6386 + 1G>A), along with two mutations identified once during the initial HRM screen (p.G1127E, and p.K2160E). Login to comment 68 ABCA4 p.Lys2160Glu ABCA4 p.Leu510Arg ABCA4 p.Gly1127Glu Three of the four recurrent mutations were identified (p.L510R, c.2408delG and c.6386ߙ +ߙ 1G>A), along with two mutations identified once during the initial HRM screen (p.G1127E, and p.K2160E). Login to comment 76 ABCA4 p.Gly863Ala ABCA4 p.Asn965Ser ABCA4 p.Leu510Arg Among the novel mutations detected, the four p.L510R-carrying alleles are found in the Stargardt-flavimaculatus group in combination with p.G863A, p.2030Q, and the Danish founder mutation p.N965S (Table 4). Login to comment 77 ABCA4 p.Asn965Ser In the generalized retinal dystrophy group the three c.2408delG mutations are found in combination with c.3191-2A>G and N965S. Login to comment 78 ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Asn965Ser ABCA4 p.Trp1551* ABCA4 p.Leu510Arg The stop mutation p.W1551X is combined with the mild mutation p.G863A though resulting in a serious phenotype. Login to comment 79 ABCA4 p.Asn965Ser In the generalized retinal dystrophy group the three c.2408delG mutations are found in combination with c.3191-2A>G and N965S. Login to comment 80 ABCA4 p.Gly863Ala ABCA4 p.Trp1551* The stop mutation p.W1551X is combined with the mild mutation p.G863A though resulting in a serious phenotype. Login to comment 89 ABCA4 p.Phe655Cys ABCA4 p.Lys2160Glu ABCA4 p.Ala1357Thr ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Gly1127Glu ABCA4 p.Arg1898His ABCA4 p.Thr1415Pro ABCA4 p.Asn965Lys ABCA4 p.Val552Ile Encouraged by the result and the identification Table 2 Mutations identified by selected HRM screening of 30 patients without Asper-mutations Patient DNA Protein Exon/intron Ref D015 c.3380G>A p.G1127E 23 New* c.6478A>G p.K2160E 47 New* c.1654G>A p.V552I 12 29 D048 c.3765_3766dupTG na 25 New c.5693G>A p.R1898H 40 28 c.1964T>G p.F655C 14 30 D128 c.2408delG na 16 New* c.4243A>C p.T1415P 28 New D133 c.1529T>G p.L510R 11 New* c.6386 + 1G>A na 46 New* D061 c.1529T>G p.L510R 11 New* D102 c.2895T>G p.N965K 19 New D183 c.4069G>A p.A1357T 27 New D190 c.2408delG na 16 New* na; not applicable, *Identified during the initial mutation screen. Login to comment 91 ABCA4 p.Phe655Cys ABCA4 p.Lys2160Glu ABCA4 p.Ala1357Thr ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Gly1127Glu ABCA4 p.Arg1898His ABCA4 p.Thr1415Pro ABCA4 p.Asn965Lys ABCA4 p.Val552Ile Encouraged by the result and the identification Table 2ߒ Mutations identified by selected HRM screening of 30 patients without Asper-mutations Patient DNA Protein Exon/intron Ref D015 c.3380G>A p.G1127E 23 New* c.6478A>G p.K2160E 47 New* c.1654G>A p.V552I 12 29 D048 c.3765_3766dupTG na 25 New c.5693G>A p.R1898H 40 28 c.1964T>G p.F655C 14 30 D128 c.2408delG na 16 New* c.4243A>C p.T1415P 28 New D133 c.1529T>G p.L510R 11 New* c.6386ߙ+ߙ1G>A na 46 New* D061 c.1529T>G p.L510R 11 New* D102 c.2895T>G p.N965K 19 New D183 c.4069G>A p.A1357T 27 New D190 c.2408delG na 16 New* na; not applicable, *Identified during the initial mutation screen. Login to comment 97 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Cys1488Arg ABCA4 p.Cys1490Tyr ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Phe655Cys ABCA4 p.Val767Asp ABCA4 p.Arg1108Cys ABCA4 p.Arg2030Gln ABCA4 p.Arg2030Gln ABCA4 p.Arg2030Gln ABCA4 p.Lys2160Glu ABCA4 p.Lys2160Glu ABCA4 p.Ala1357Thr ABCA4 p.Cys748Tyr ABCA4 p.Cys2150Tyr ABCA4 p.Phe608Leu ABCA4 p.Thr972Asn ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys ABCA4 p.Leu1246Val ABCA4 p.Gly550Arg ABCA4 p.Gly1127Glu ABCA4 p.Pro62Ser ABCA4 p.Leu1580Ser ABCA4 p.Thr901Ala ABCA4 p.Leu2033Arg ABCA4 p.Arg1898His ABCA4 p.Arg1898His ABCA4 p.Thr1415Pro ABCA4 p.Val552Ile ABCA4 p.Gly1127Lys Phenotype Patient Mutation 1 Mutation 2 Mutation 3 Stargardt-flavimaculatus D043 p.G863A p.P62S D050 p.G863A p.L510R D112 p.N965S p.L510R D069 p.A1038V p.L510R D099 p.R2030Q p.L510R D178 p.A1038V c.1843_1844delRG D166 p.G863A p.V767D D191 p.G863A p.A1357T D167 c.5461-10T>C p.R1368C D128 p.2408delG* p.T1415P D027 p.G863A c.4668-2A>G* D136 p.[L541P+A1038V] p.L1580S D048 c.3766dupTG* p.R1898H p.F655C D034 p.G863A c.4773 + 5G>A* D015 p. G1127K p.K2160E p.V552I D189 p.N965S p.K2160E D433 p.G1961E c.6005 + 1G>A* Generalized retinal dystrophy D117 c.3191-2A>G* c.2408delG* D135 p.N965S c.2408delG* D147 p.N965S c.2408delG* D173 p.C1490Y p.T972N D018 p.C2150Y p.L1246V D022 p.C1488R p.R1368C D108 p.G550R p.R1368C D414 p.G863A p.W1551X* D444 p.T901A c.4773 + 3A>G* D110 p.[L541P+A1038V] c.5584 + 1G>A* D182 p.R2030Q c.6386 + 1G>A* D186 p.R1108C c.6386 + 1G>AA* D133 p.L510R IVS46 + 1G>A* Cone-rod dystrophy D134 c.4667 + 2G>T* p.L2033R Atypical maculopathy D165 p.F608L p.C748Y D181 p.R2030Q p.G1127E D188 c.5461-10T>C p.R1898H *Predicted to compromise correct reading frame. Login to comment 99 ABCA4 p.Asn965Ser We have previously found the known p.N965S (c.2894A>G) mutation to account for 16.2% of the pathogenic alleles among patients of Danish origin,9 and together with the four new prevalent mutations, these five mutations account for 20% (49/240) of the pathogenic alleles. Login to comment 100 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Cys1488Arg ABCA4 p.Cys1490Tyr ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Phe655Cys ABCA4 p.Val767Asp ABCA4 p.Arg1108Cys ABCA4 p.Arg2030Gln ABCA4 p.Arg2030Gln ABCA4 p.Arg2030Gln ABCA4 p.Lys2160Glu ABCA4 p.Lys2160Glu ABCA4 p.Ala1357Thr ABCA4 p.Cys748Tyr ABCA4 p.Cys2150Tyr ABCA4 p.Phe608Leu ABCA4 p.Thr972Asn ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Leu510Arg ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys ABCA4 p.Leu1246Val ABCA4 p.Gly550Arg ABCA4 p.Gly1127Glu ABCA4 p.Pro62Ser ABCA4 p.Leu1580Ser ABCA4 p.Thr901Ala ABCA4 p.Leu2033Arg ABCA4 p.Arg1898His ABCA4 p.Arg1898His ABCA4 p.Thr1415Pro ABCA4 p.Val552Ile ABCA4 p.Gly1127Lys Phenotype Patient Mutation 1 Mutation 2 Mutation 3 Stargardt-flavimaculatus D043 p.G863A p.P62S D050 p.G863A p.L510R D112 p.N965S p.L510R D069 p.A1038V p.L510R D099 p.R2030Q p.L510R D178 p.A1038V c.1843_1844delRG D166 p.G863A p.V767D D191 p.G863A p.A1357T D167 c.5461-10T>C p.R1368C D128 p.2408delG* p.T1415P D027 p.G863A c.4668-2A>G* D136 p.[L541P+A1038V] p.L1580S D048 c.3766dupTG* p.R1898H p.F655C D034 p.G863A c.4773ߙ+ߙ5G>A* D015 p. G1127K p.K2160E p.V552I D189 p.N965S p.K2160E D433 p.G1961E c.6005ߙ+ߙ1G>A* Generalized retinal dystrophy D117 c.3191-2A>G* c.2408delG* D135 p.N965S c.2408delG* D147 p.N965S c.2408delG* D173 p.C1490Y p.T972N D018 p.C2150Y p.L1246V D022 p.C1488R p.R1368C D108 p.G550R p.R1368C D414 p.G863A p.W1551X* D444 p.T901A c.4773ߙ+ߙ3A>G* D110 p.[L541P+A1038V] c.5584ߙ+ߙ1G>A* D182 p.R2030Q c.6386ߙ+ߙ1G>A* D186 p.R1108C c.6386ߙ+ߙ1G>AA* D133 p.L510R IVS46ߙ+ߙ1G>A* Cone-rod dystrophy D134 c.4667ߙ+ߙ2G>T* p.L2033R Atypical maculopathy D165 p.F608L p.C748Y D181 p.R2030Q p.G1127E D188 c.5461-10T>C p.R1898H *Predicted to compromise correct reading frame. Login to comment 101 ABCA4 p.Ala1038Val We have previously shown that the mutation spectrum of recessive diseases in the Danish population can be quite different from populations in central Europe.21,22 A similar diverse ABCA4 mutation spectrum has been described for other European populations.14,16 Patient D013 was by array analysis solely found to be heterozygous for the common p.P541L mutation, which usually is allelic to p.A1038V. Login to comment 102 ABCA4 p.Ala1038Val ABCA4 p.Asn965Ser In fact p.[P541L+A1038V] was the third most common allele in our initial array analysis and is one of the most prevalent European mutations.23 HRM identified p.A1038V as the second mutation in D013, thus this mutation was missed by array analysis, and the patient is most likely "only" a carrier for the p.[P541L+A1038V]. Login to comment 104 ABCA4 p.Ala1038Val We have previously shown that the mutation spectrum of recessive diseases in the Danish population can be quite different from populations in central Europe.21,22 A similar diverse ABCA4 mutation spectrum has been described for other European populations.14,16 Patient D013 was by array analysis solely found to be heterozygous for the common p.P541L mutation, which usually is allelic to p.A1038V. Login to comment 105 ABCA4 p.Ala1038Val ABCA4 p.Lys2160Glu ABCA4 p.Gly1127Glu ABCA4 p.Val552Ile In sample D015 the known p.V552I mutation was identified along with the newly identified p.K2160E and p.G1127E variations. Login to comment 106 ABCA4 p.Lys2160Glu ABCA4 p.Gly1127Glu In silico analysis with three different algorithms all predicted the clear pathogenic variations of p.G1127E and p.K2160E. Login to comment 108 ABCA4 p.Lys2160Glu ABCA4 p.Gly1127Glu ABCA4 p.Val552Ile In sample D015 the known p.V552I mutation was identified along with the newly identified p.K2160E and p.G1127E variations. Login to comment 109 ABCA4 p.Phe655Cys ABCA4 p.Lys2160Glu ABCA4 p.Gly1127Glu ABCA4 p.Arg1898His The newly identified c.3766dupTG clearly disrupts the protein function and together with the known p.R1898H and p.F655C mutations confirm the diagnosis genetically. Login to comment 112 ABCA4 p.Phe655Cys ABCA4 p.Arg1898His The newly identified c.3766dupTG clearly disrupts the protein function and together with the known p.R1898H and p.F655C mutations confirm the diagnosis genetically. Login to comment 120 ABCA4 p.Ala1038Val ABCA4 p.Arg1098Cys The remaining two patients were heterozygous for the known p.A1038V and p.R1098C mutations, respectively. Login to comment 121 ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys In one of the solely heterozygous c.5461-10C>T patients the new recurrent p.R1368C mutations was identified (patients D167), however c.5461-10C>T was not detected in combination with p.R1368C in other patients. Login to comment 122 ABCA4 p.Arg1898His Patient D188 was likewise initially solely heterozygous for c.5461-10C>T, but turned out to also harbor the p.R1898H mutation. Login to comment 123 ABCA4 p.Ala1038Val ABCA4 p.Arg1098Cys The remaining two patients were heterozygous for the known p.A1038V and p.R1098C mutations, respectively. Login to comment 124 ABCA4 p.Arg1368Cys ABCA4 p.Arg1368Cys In one of the solely heterozygous c.5461-10C>T patients the new recurrent p.R1368C mutations was identified (patients D167), however c.5461-10C>T was not detected in combination with p.R1368C in other patients. Login to comment 125 ABCA4 p.Arg1898His Patient D188 was likewise initially solely heterozygous for c.5461-10C>T, but turned out to also harbor the p.R1898H mutation. Login to comment