ABCMdb

PMID: 15375183

Wang J, Joy T, Mymin D, Frohlich J, Hegele RA
Phenotypic heterogeneity of sitosterolemia.
J Lipid Res. 2004 Dec;45(12):2361-7. Epub 2004 Sep 16., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCG8 p.Ser107* We report five Canadian subjects with nonsense mutations in these half-transporters: four related Caucasian subjects were homozygous for the ABCG8 S107X mutation, and one unrelated Japanese-Canadian subject was homozygous for a complex insertion/deletion (I/D) mutation in ABCG5 exon 3. Login to comment 3 ABCG8 p.Ser107* ABCG8 p.Ser107* We report five Canadian subjects with nonsense mutations in these half-transporters: four related Caucasian subjects were homozygous for the ABCG8 S107X mutation, and one unrelated Japanese-Canadian subject was homozygous for a complex insertion/deletion (I/D) mutation in ABCG5 exon 3. Login to comment 4 ABCG8 p.Ser107* A female subject with each mutation was symptomatic with coronary atherosclerosis: a 5-year-old ABCG8 S107X homozygote and a 75-year-old ABCG5 exon 3 I/D homozygote; these represent the extreme ends of the spectrum of vascular involvement in sitosterolemia. Login to comment 32 ABCG8 p.Ser107* METHODS Study subjects Family 1: ABCG8 S107X subjects II-1 to II-4. Login to comment 34 ABCG8 p.Ser107* METHODS Study subjects Family 1: ABCG8 S107X subjects II-1 to II-4. Login to comment 85 ABCG8 p.Ser107* RESULTS Clinical and biochemical attributes From the ABCG8 S107X kindred, subjects II-1 to II-4 each had high LDL-cholesterol and low HDL-cholesterol, with corresponding changes in apolipoprotein A-I (apoA-I) and apoB concentrations. Login to comment 87 ABCG8 p.Ser107* RESULTS Clinical and biochemical attributes From the ABCG8 S107X kindred, subjects II-1 to II-4 each had high LDL-cholesterol and low HDL-cholesterol, with corresponding changes in apolipoprotein A-I (apoA-I) and apoB concentrations. Login to comment 100 ABCG8 p.Ser107* Sequencing showed that the two younger siblings and the first cousin were also homozygous for the S107X mutation, whereas both parents were heterozygous. Login to comment 101 ABCG8 p.Ser107* Additional sequence analyses showed that the ABCG8 S107X mutation was absent from the genomic DNA of 360 healthy Caucasians. Login to comment 102 ABCG8 p.Ser107* Sequencing showed that the two younger siblings and the first cousin were also homozygous for the S107X mutation, whereas both parents were heterozygous. Login to comment 103 ABCG8 p.Ser107* Additional sequence analyses showed that the ABCG8 S107X mutation was absent from the genomic DNA of 360 healthy Caucasians. Login to comment 106 ABCG8 p.Ser107* Each of four Caucasian subjects with the ABCG8 S107X mutation, which encodes a protein that is truncated by 80%, was ascertained under age 10 and had profound hyperlipidemia, with the index case showing marked skin manifestations and premature severe atherosclerosis with CHD. Login to comment 108 ABCG8 p.Ser107* ABCG8 p.Ser107* Each of four Caucasian subjects with the ABCG8 S107X mutation, which encodes a protein that is truncated by ~80%, was ascertained under age 10 and had profound hyperlipidemia, with the index case showing marked skin manifestations and premature severe atherosclerosis with CHD. Login to comment 109 ABCG8 p.Ser107* In the surviving ABGC8 S107X homozygotes, treatment with ezetimibe or bile acid sequestrants caused the largest reductions of plasma LDL cholesterol and sitosterol, whereas treatment with statin drugs was associated with less LDL-cholesterol reduction. Login to comment 110 ABCG8 p.Ser107* One subject with each mutation was symptomatic with coronary atherosclerosis: a 5 year old girl with the ABCG8 S107X mutation and a 75 year old woman with the ABCG5 exon 3 I/D mutation, who represent the extreme ends of the spectrum of vascular involvement in sitosterolemia. Login to comment 111 ABCG8 p.Ser107* In the surviving ABGC8 S107X homozygotes, treatment with ezetimibe or bile acid sequestrants caused the largest reductions of plasma LDL cholesterol and sitosterol, whereas treatment with statin drugs was associated with less LDL-cholesterol reduction. Login to comment 113 ABCG5 p.Arg389His In this ethnic group, ABCG5 exon 9 is most commonly affected, and the most common mutation is R389H. Login to comment 115 ABCG5 p.Arg389His In this ethnic group, ABCG5 exon 9 is most commonly affected, and the most common mutation is R389H. Login to comment 121 ABCG8 p.Ser107* Subjects ABCG8 S107X II-1 to II-4 demonstrated a certain degree of clinical and biochemical heterogeneity (Table 2), of which the most dramatic were the cardiac and skin manifestations in subject II-1. Login to comment 123 ABCG8 p.Ser107* Subjects ABCG8 S107X II-1 to II-4 demonstrated a certain degree of clinical and biochemical heterogeneity (Table 2), of which the most dramatic were the cardiac and skin manifestations in subject II-1. Login to comment 125 ABCG8 p.Ser107* Interestingly, the parents of the proband, both of whom were heterozygotes for ABCG8 S107X, had some biochemical disparities. Login to comment 127 ABCG8 p.Ser107* Interestingly, the parents of the proband, both of whom were heterozygotes for ABCG8 S107X, had some biochemical disparities. Login to comment