ABCMdb

PMID: 22427542

Fritsche LG, Fleckenstein M, Fiebig BS, Schmitz-Valckenberg S, Bindewald-Wittich A, Keilhauer CN, Renner AB, Mackensen F, Mossner A, Pauleikhoff D, Adrion C, Mansmann U, Scholl HP, Holz FG, Weber BH
A subgroup of age-related macular degeneration is associated with mono-allelic sequence variants in the ABCA4 gene.
Invest Ophthalmol Vis Sci. 2012 Apr 30;53(4):2112-8. doi: 10.1167/iovs.11-8785. Print 2012 Apr., [PubMed]

Sentences

No. Mutations Sentence Comment

69 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro ABCA4 p.Glu1087Asp The heterozygous change c.3113C>T (p.A1038V) was found in five patients together with c.1622T>C (p.L541P) and in another two patients together with c.3261A>C (p.E1087D, patient L-099-GA) and c.3752delA (p.E1251fs, patient H-144-GA), respectively. Login to comment 71 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro ABCA4 p.Glu1087Asp The heterozygous change c.3113C>T (p.A1038V) was found in five patients together with c.1622T>C (p.L541P) and in another two patients together with c.3261A>C (p.E1087D, patient L-099-GA) and c.3752delA (p.E1251fs, patient H-144-GA), respectively. Login to comment 82 ABCA4 p.Gly863Ala Upper row: Right and left eye of a female patient (age of onset 46 years) with autosomal recessive STGD1 genetically confirmed by two ABCA4 variants (c.2588G>C, p.G863A/p.G863del and c.4234C>T, p.E1412X). Login to comment 84 ABCA4 p.Gly863Ala Upper row: Right and left eye of a female patient (age of onset 46 years) with autosomal recessive STGD1 genetically confirmed by two ABCA4 variants (c.2588G>C, p.G863A/p.G863del and c.4234C>T, p.E1412X). Login to comment 86 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro The patient carries a heterozygous, complex disease allele (c.1622T>C, p.L541P; c.3113C>T, p.A1038V) in the ABCA4 gene. Login to comment 87 ABCA4 p.Ala1038Val ABCA4 p.Glu1087Asp directly the cis configuration of the c.3113C>T / c.1622T>C alleles in one case by segregation analysis (patient M07-0338- 11,085), these two variants have been shown repeatedly in previous studies to occur as a frequent complex allele on a single chromosome.10,36 Trans-configuration was confirmed for heterozygous changes c.3113C>T (p.A1038V) / c.3261A>C (p.E1087D) in patient L-099-GA. Login to comment 88 ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro ABCA4 p.Arg602Trp ABCA4 p.Val643Gly The patient carries a heterozygous, complex disease allele (c.1622T>C, p.L541P; c.3113C>T, p.A1038V) in the ABCA4 gene. Login to comment 89 ABCA4 p.Ala1038Val ABCA4 p.Glu1087Asp directly the cis configuration of the c.3113C>T / c.1622T>C alleles in one case by segregation analysis (patient M07-0338- 11,085), these two variants have been shown repeatedly in previous studies to occur as a frequent complex allele on a single chromosome.10,36 Trans-configuration was confirmed for heterozygous changes c.3113C>T (p.A1038V) / c.3261A>C (p.E1087D) in patient L-099-GA. Login to comment 90 ABCA4 p.Ala1038Val ABCA4 p.Arg602Trp ABCA4 p.Val643Gly Due to lack of DNA from further family members, segregation of variants c.3113C>T (p.A1038V) / c.3752delA (p.Glu1251fs) and c.1804C>T (p.R602W) / c.1928T>G (p.V643G) could not be assessed further (Supplementary Table S5). Login to comment 91 ABCA4 p.Arg212Cys ABCA4 p.Val2050Leu ABCA4 p.Thr1519Arg These patients were heterozygous for variants c.634C>T (p.R212C), c.4556C>G (p.T1519R), and c.6148G>C (p.V2050L), respectively. Login to comment 93 ABCA4 p.Arg212Cys ABCA4 p.Val2050Leu ABCA4 p.Thr1519Arg These patients were heterozygous for variants c.634C>T (p.R212C), c.4556C>G (p.T1519R), and c.6148G>C (p.V2050L), respectively. Login to comment 98 ABCA4 p.Asn1868Ile In contrast, variant c.5603A>T (p.N1868I) was significantly enriched in GPS[+] and STGD1 patients, in agreement with previous findings that have led to the suggestion that the polymorphic variant c.5603A>T may act as a risk-increasing factor in ABCA4-related pathology.37 Together, these data strongly suggest that there is no founder effect in the GPS[+] group as frequencies in the common sequence variants of the ABCA4 gene are not different from the GPS[+] group and the European-American NHLBI samples. Login to comment 100 ABCA4 p.Asn1868Ile In contrast, variant c.5603A>T (p.N1868I) was significantly enriched in GPS[+] and STGD1 patients, in agreement with previous findings that have led to the suggestion that the polymorphic variant c.5603A>T may act as a risk-increasing factor in ABCA4-related pathology.37 Together, these data strongly suggest that there is no founder effect in the GPS[+] group as frequencies in the common sequence variants of the ABCA4 gene are not different from the GPS[+] group and the European-American NHLBI samples. Login to comment 118 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro In this context, it may be of interest that the complex allele L541P/ A1038V was found in 5/20 GPS[+] alleles. Login to comment 119 ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val If one further includes the single A1038V variant, which was found twice in GPS[+], there is a striking overabundance of A1038V alleles in GPS[+] (35% of all alleles identified). Login to comment 120 ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro In this context, it may be of interest that the complex allele L541P/ A1038V was found in 5/20 GPS[+] alleles. Login to comment 121 ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val If one further includes the single A1038V variant, which was found twice in GPS[+], there is a striking overabundance of A1038V alleles in GPS[+] (35% of all alleles identified). Login to comment 122 ABCA4 p.Ala1038Val Although the GPS[+] patient group is small in number and, therefore, prone to random findings, our data may still point to the possibility that only a certain type of variant, such as A1038V, could be associated with the GPS[+] phenotype. Login to comment 132 ABCA4 p.Asn1868Ile In addition, our analysis of common variant frequencies in the ABCA4 gene showed that c.5603A>T (p.N1868I) is enriched greatly in the GPS[+] group, a variant that has been suggested previously to act as a risk-increasing factor in ABCA4-related pathology.37 Our findings were in accordance with the genotype-phenotype model suggested by Maugeri et al.,7 proposing pathological effects dependent on a threshold of physiological ABCA4 activity. Login to comment 134 ABCA4 p.Asn1868Ile In addition, our analysis of common variant frequencies in the ABCA4 gene showed that c.5603A>T (p.N1868I) is enriched greatly in the GPS[+] group, a variant that has been suggested previously to act as a risk-increasing factor in ABCA4-related pathology.37 Our findings were in accordance with the genotype-phenotype model suggested by Maugeri et al.,7 proposing pathological effects dependent on a threshold of physiological ABCA4 activity. Login to comment