ABCMdb

PMID: 15790791

Albrecht C, McVey JH, Elliott JI, Sardini A, Kasza I, Mumford AD, Naoumova RP, Tuddenham EG, Szabo K, Higgins CF
A novel missense mutation in ABCA1 results in altered protein trafficking and reduced phosphatidylserine translocation in a patient with Scott syndrome.
Blood. 2005 Jul 15;106(2):542-9. Epub 2005 Mar 24., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCA1 p.Arg1925Gln The SS patient was heterozygous for a novel missense mutation c.6064G>A (ABCA1 R1925Q), absent from unaffected family members and controls. Login to comment 4 ABCA1 p.Arg1925Gln The SS patient was heterozygous for a novel missense mutation c.6064G>A (ABCA1 R1925Q), absent from unaffected family members and controls. Login to comment 5 ABCA1 p.Arg1925Gln In vitro expression studies showed impaired trafficking of ABCA1 R1925Q to the plasma membrane. Login to comment 6 ABCA1 p.Arg1925Gln In vitro expression studies showed impaired trafficking of ABCA1 R1925Q to the plasma membrane. Login to comment 114 ABCA1 p.Arg1925Gln The R1925Q variant was not found in 164 alleles of a control population of British origin,32 evidenced by WAVE analysis. Login to comment 115 ABCA1 p.Arg219Lys ABCA1 p.Arg1925Gln The R1925Q variant was not found in 164 alleles of a control population of British origin,32 evidenced by WAVE analysis. Login to comment 116 ABCA1 p.Arg219Lys For comparison, the allele frequency of the polymorphism in exon 6 (R219K) in this population was 0.22, similar to that observed in other European populations (0.254).33 To investigate whether there was differential expression of the 2 alleles, a PCR product spanning the c.6064GϾA mutation was generated by RT-PCR from total RNA isolated from leukocytes of 544 ALBRECHT et al BLOOD, 15 JULY 2005 the SS patient. Login to comment 121 ABCA1 p.Arg1925Gln Localization studies To test the impact of the R1925Q mutation on intracellular trafficking of ABCA1, we introduced the c.6064Gb0e;A mutation into a full-length cDNA encoding ABCA1 fused at its carboxyterminus to EGFP, and expressed the fusion protein in HEK 293 Figure 1. Login to comment 122 ABCA1 p.Arg1925Gln Localization studies To test the impact of the R1925Q mutation on intracellular trafficking of ABCA1, we introduced the c.6064GϾA mutation into a full-length cDNA encoding ABCA1 fused at its carboxyterminus to EGFP, and expressed the fusion protein in HEK 293 Figure 1. Login to comment 148 ABCA1 p.Arg1925Gln In contrast, little or no fluorescence was detected on the surface of cells transfected with the ABCA1 R1925Q-EGFP construct (Figure 4A middle and right panels; Figure 4B left panel). Login to comment 149 ABCA1 p.Arg1925Gln In contrast, little or no fluorescence was detected on the surface of cells transfected with the ABCA1 R1925Q-EGFP construct (Figure 4A middle and right panels; Figure 4B left panel). Login to comment 157 ABCA1 p.Arg1925Gln The mutated residue (ABCA1 R1925Q) is indicated by a rectangle. Login to comment 158 ABCA1 p.Arg1925Gln The mutated residue (ABCA1 R1925Q) is indicated by a rectangle. Login to comment 162 ABCA1 p.Arg1925Gln (A) Confocal sections of transiently transfected HEK 293 cells expressing wild-type ABCA1-EGFP (left) and ABCA1 R1925Q-EGFP (middle and right). Login to comment 163 ABCA1 p.Arg1925Gln (A) Confocal sections of transiently transfected HEK 293 cells expressing wild-type ABCA1-EGFP (left) and ABCA1 R1925Q-EGFP (middle and right). Login to comment 165 ABCA1 p.Arg1925Gln (B) HEK 293 cells expressing wild-type ABCA1-EGFP and ABCA1 R1925Q-EGFP were stained for SERCA 2 (red) as marker for the ER. The same confocal sections are shown for EGFP (green, left column), SERCA 2 (red, middle column) and colocalization of EGFP and SERCA2 in the overlay (yellow, right column). Login to comment 166 ABCA1 p.Arg1925Gln ABCA1 p.Arg1925Gln (B) HEK 293 cells expressing wild-type ABCA1-EGFP and ABCA1 R1925Q-EGFP were stained for SERCA 2 (red) as marker for the ER. The same confocal sections are shown for EGFP (green, left column), SERCA 2 (red, middle column) and colocalization of EGFP and SERCA2 in the overlay (yellow, right column). Login to comment 167 ABCA1 p.Arg1925Gln Colocalization of ABCA1-SERCA2 was observed in cells transfected with mutant ABCA1, implying retention of R1925Q in the ER. In contrast, wild-type ABCA1-EGFP localized predominantly to the plasma membrane and no colocalization was detected. Login to comment 177 ABCA1 p.Arg1925Gln We identified a novel missense mutation in ABCA1 (R1925Q) in the SS patient, which results in severely impaired trafficking and reduced expression of functional ABCA1 protein at the cell surface. Login to comment 179 ABCA1 p.Arg1925Gln We identified a novel missense mutation in ABCA1 (R1925Q) in the SS patient, which results in severely impaired trafficking and reduced expression of functional ABCA1 protein at the cell surface. Login to comment