ABCMdb

PMID: 20018285

Pisciotta L, Tarugi P, Borrini C, Bellocchio A, Fresa R, Guerra D, Quaglino D, Ronchetti I, Calandra S, Bertolini S
Pseudoxanthoma elasticum and familial hypercholesterolemia: a deleterious combination of cardiovascular risk factors.
Atherosclerosis. 2010 May;210(1):173-6. Epub 2009 Nov 24., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC6 p.Arg1141* ABCC6 p.Ser317Arg Results and conclusions: The patient was a compound heterozygous for two ABCC6 mutations (p.S317R and p.R1141X) and heterozygous for a novel LDLR mutation (p.R574H). Login to comment 28 ABCC6 p.Arg1141* ABCC6 p.Ser317Arg The proband, indicated by an arrow, was a compound heterozygous for the following ABCC6 gene mutations: (i) c.951 C > A in exon 8 (p.S317R); (ii) c.3421 C > T in exon 24 (p.R1141X). Login to comment 45 ABCC6 p.Arg1141* ABCC6 p.Ser317Arg Subject (gender) I.1 (F) I.2 (F) I.3 (F) II.1 (F) II.2 (F) II.3 (M) III.1 (F) III.2 (F) III.3 (M) ABCC6 genotype M1/M2 W/M2 W/W W/M1 W/M1 W/M1 W/M1 W/W W/M1 LDLR genotype W/M3 W/W W/W W/M3 W/M3 W/M3 W/W W/M3 W/M3 Age (years) 60 56 34 40 39 36 7 15 8 BMI (kg/m2 ) 24.9 20.5 24.1 20.8 23.4 28.3 17.7 19.9 13.6 TC (mmol/L) 11.50 ± 0.59 7.88 5.53 8.22 7.03 7.19 4.55 5.74 5.71 LDL-C (mmol/L) 9.08 ± 0.54 5.44 3.29 4.96 4.78 5.22 2.75 3.75 3.77 HDL-C (mmol/L) 1.70 ± 0.16 2.01 1.83 2.66 1.89 0.90 1.55 1.52 1.68 TG (mmol/L) 1.93 ± 0.30 0.92 0.87 1.32 0.77 2.31 0.53 1.03 0.57 ApoA-I (mg/dL) 173 ± 10 209 202 226 182 112 192 183 194 ApoB (mg/dL) 246 ± 13 144 97 132 122 135 68 92 95 APOE genotype ␧3␧3 ␧3␧3 ␧3␧3 ␧2␧3 ␧3␧4 ␧2␧3 ␧2␧3 ␧3␧3 ␧3␧4 Values are mean ± SD; all values are before pharmacological treatment; ABCC6 genotype: W = wild type, M1 = c.951 C > A (p.S317R), M2 = c.3421 C > T (p.R1141X); LDLR genotype: W = wild type, M3 = c.1721 G > A (p.R574H). Login to comment 50 ABCC6 p.Arg1141* ABCC6 p.Ser317Arg Sequence of ABCC6 gene The proband was compound heterozygous for mutations in ABCC6 gene: (i) a C > A transversion in exon 8 (c.951 C > A), which results in arginine for serine conversion at position 317 (p.S317R); (ii) a C > T transition in exon 24 (c.3421 C > T), which converts arginine codon at position 1141 into a termination codon (p.R1141X). Login to comment 51 ABCC6 p.Arg1141* One of the proband`s sisters (subject I.2) was a carrier of the p.R1141X mutation. Login to comment 52 ABCC6 p.Ser317Arg The proband`s three offspring and two of the grandchildren were carriers of p.S317R mutation (Fig. 1). Login to comment 61 ABCC6 p.Ser317Arg In silico analysis of the ABCC6 and LDLR missense mutations The ABCC6 p.S317R mutation resulted to be "possibly damaging" according to PolyPhen and "pathogenic" according to PANTHER, but was predicted to be "tolerated" according to SIFT. Login to comment 64 ABCC6 p.Arg1141* ABCC6 p.Ser317Arg Screening for the ABCC6 mutations Both mutations, p.S317R and p.R1141X, were screened in 106 healthy controls. Login to comment 66 ABCC6 p.Arg1141* The p.R1141X was also screened in 173 patients with premature CAD (before 55 years in males and 65 years in females) (Supplementary Table 1) Three carriers (two males and one female) were found among subjects of this group (1.7%). Login to comment 84 ABCC6 p.Arg1141* In this context it is noteworthy the observation that the frequency of the p.R1141X mutation of ABCC6 gene (the most common mutation in PXE) was found to be increased (3.3% vs. 0.8%) in a large group of patients with premature coronary heart disease [8]. Login to comment