ABCMdb

PMID: 10634626

Souied EH, Ducroq D, Rozet JM, Gerber S, Perrault I, Munnich A, Coscas G, Soubrane G, Kaplan J
ABCR gene analysis in familial exudative age-related macular degeneration.
Invest Ophthalmol Vis Sci. 2000 Jan;41(1):244-7., [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.Ser2255Ile ABCA4 p.Val1433Ile A lack of familial segregation was observed in 4 of 6 codon changes (Arg943Gln, Val1433Ile, Pro1948Leu, and Ser2255Ile). Login to comment 9 ABCA4 p.Leu1970Phe ABCA4 p.Pro940Arg Conversely, 2 codon changes cosegregated with the disease in 2 small families: Pro940Arg and Leu1970Phe. Login to comment 40 ABCA4 p.Leu1970Phe ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.Ser2255Ile ABCA4 p.Val1433Ile ABCA4 p.Pro940Arg The heterozygous codon changes observed were Pro940Arg, Arg943Gln (2 families), Pro1948Leu (2 families), Leu1970Phe, Val1433Ile, and Ser2255Ile. Login to comment 41 ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.Ser2255Ile The Arg943Gln, Pro1948Leu, and Ser2255Ile substitutions were observed in the control group: in 3 of 90, 3 of 90, and 1 of 90, respectively. Login to comment 42 ABCA4 p.Leu1970Phe ABCA4 p.Val1433Ile ABCA4 p.Pro940Arg Conversely, the Pro940Arg, Val1433Ile, and Leu1970Phe changes were not found in the control group. Login to comment 43 ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.Ser2255Ile ABCA4 p.Val1433Ile No cosegregation of the base substitution with the disease was observed in the families harboring either Arg943Gln, Val1433Ile, Pro1948Leu, or Ser2255Ile changes. Login to comment 45 ABCA4 p.Pro1948Leu It is worth noting that the Pro1948Leu codon change seen in a patient belonging to a large family (13 siblings were alive and analyzed) did not segregate with the disease. Login to comment 48 ABCA4 p.Leu1970Phe ABCA4 p.Pro940Arg An association of the mutations with the disease was observed in the 2 small families harboring 2 mutations absent in controls: Pro940Arg and Leu1970Phe (Fig. Login to comment 53 ABCA4 p.Arg943Gln ABCA4 p.Ser2255Ile In these studies, the Arg943Gln and Ser2255Ile codon changes have been reported as polymorphisms. Login to comment 54 ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.Ser2255Ile Here, the lack of detection of Arg943Gln, Pro1948Leu, and Ser2255Ile in controls was not particularly meaningful and did not permit us to establish statistical significance. Login to comment 56 ABCA4 p.Leu1970Phe ABCA4 p.Pro940Arg Pedigrees of the 2 families presenting the Pro940Arg and Leu1970Phe codon changes. Login to comment 63 ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.Ser2255Ile ABCA4 p.Val1433Ile First, a lack of segregation was observed, for the Arg943Gln, Val1433Ile, Pro1948Leu, and Ser2255Ile changes. Login to comment 68 ABCA4 p.Val1433Ile It is worth noting that Val1433Ile, not observed in controls, was excluded only using segregation analysis. Login to comment 69 ABCA4 p.Leu1970Phe ABCA4 p.Pro940Arg Second, for Pro940Arg and Leu1970Phe we observed possible segregation with AMD. However, the families were too small to draw any definite conclusions about causality because only one generation could be analyzed. Login to comment 72 ABCA4 p.Leu1970Phe ABCA4 p.Pro940Arg The Pro940Arg and the Leu1970Phe codon changes occur in codons adjacent to the first and second ATP-binding sites, respectively. Login to comment 74 ABCA4 p.Leu1970Phe ABCA4 p.Pro940Arg The Leu1970Phe mutation has been observed in compound heterozygous Stargardt patients so that this mutation is presumed to induce important ABCR protein alterations.18 This mutation was also previously identified in one case of AMD but not observed in the general population (n ϭ 220).19 To the best of our knowledge, the Pro940Arg mutation has not been reported previously. Login to comment