ABCMdb

PMID: 20521169

Niu DM, Chong KW, Hsu JH, Wu TJ, Yu HC, Huang CH, Lo MY, Kwok CF, Kratz LE, Ho LT
Clinical observations, molecular genetic analysis, and treatment of sitosterolemia in infants and children.
J Inherit Metab Dis. 2010 Aug;33(4):437-43. Epub 2010 Jun 3., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCG5 p.Arg389His ABCG5 p.Asn437Lys ABCG5 p.Arg446* ABCG5 p.Tyr329* ABCG5 p.Gly269Arg We report clinical, biochemical, and molecular genetic observations and treatment outcomes for five Chinese children from four separate families presenting with sitosterolemia in whom we identified two new (Y329X, G269R) and three known (R446X, N437K, R389H) mutations in the ABCG5 gene. Login to comment 2 ABCG5 p.Arg389His The R389H mutation was found in 50% of alleles. Login to comment 23 ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Asn437Lys ABCG5 p.Arg446* ABCG5 p.Arg446* ABCG5 p.Tyr329* ABCG5 p.Gly269Arg Large peaks of serum plant sterols were identified by nuclear magnetic resonance (NMR) spectroscopy, but the exact concentrations of these sterols were unable to be Table 1 Baseline lipid profiles, liver enzymes, and blood cell counts of each study patient Patient no Normal values 1 2 3 4 5 Age at diagnosis 8 years 18 months 3 months 23 months 12 years Mutation (ABCG5) Y329X R389H R389H R389H R389H N437K R446X R446X R389H G269R Initial diagnostic data Cholesterol, mg/dl Total 125-240 427 705 402 640 343 Low-density-lipoprotein 60-150 346 565 304 519 263 High-density-lipoprotein 35-84 59 64 42 64 50 Total triglycerides, mg/dl 20-200 111 149 395a 98 98 Liver enzymes Alanine transaminase, U/l 5-45 10 13 45 15 44 Aspartate aminotransferase, U/l 15-55 19 31 100 31 37 Blood count Erythrocytes, count/µl 3.7×109 -5.3×109 3.35×109 4.25×109 3.98×109 4.49×109 4.46×109 Hemoglobin, g/dl 11.5-15.5 9.8 11.8 11 12.7 12.9 Mean corpuscular volume, fl 80-95 88.5 89.0 80.6 80.2 86 White blood cells, count/µl 4,500-17,500 7,200 6,900 6,700 11,200 5,200 Platelets, count/mm3 150×106 -350×106 211×106 289×106 506×106 566×106 293×106 After ezetimibe therapy Age at plant sterols analysis NA 5 years 3 years 3 year 13 year Duration of ezetimibe treatment NA 3 years 1 year 1 year 6 months Cholesterol, total (mg/dl) 125-240 NA 181 208 223 193 Sitosterol mg/dlb 0.216±0.220 (SD)c NA 7.10 9.17 7.07 6.14 Campesterol mg/dlb 0.309±0.165 (SD)c NA 3.79 4.78 4.04 4.22 NA not available a In the nonfasting state b Plant sterols were measured by gas chromatography/mass spectrometry, as previously described (Kwiterovich et al. 2003). Login to comment 75 ABCG5 p.Asn437Lys ABCG5 p.Tyr329* Results of mutation analyses Patient 1 had compound heterozygous mutations, p.Y329X and p.N437K. Login to comment 76 ABCG5 p.Tyr329* The new mutation, p.Y329X (c.987C>A), located in exon 8, substituted an amino acid codon (tyrosine) to a stop codon at codon 329. Login to comment 77 ABCG5 p.Asn437Lys The other mutation, N437K (c.1311C>G), located in exon 9, substituted an asparagine to a lysine at codon 437. Login to comment 79 ABCG5 p.Arg389His ABCG5 p.Arg446* Patients 2 and 3 also had compound heterozygous mutations (R389H and R446X). Login to comment 80 ABCG5 p.Arg389His R389H (c.1166G>A), located in exon 9, caused an arginine to be replaced by a histidine at codon 389. Login to comment 82 ABCG5 p.Arg446* R446X (c.1336C>T), located at exon 10, substituted an arginine codon for a stop codon at codon 446. Login to comment 84 ABCG5 p.Arg389His Patient 4 had a homozygous mutation, R389H. Login to comment 85 ABCG5 p.Arg389His ABCG5 p.Gly269Arg Patient 5 had compound heterozygous mutations, p.R389H and p.G269R. Login to comment 86 ABCG5 p.Gly269Arg The p.G269R (c.850G>A) mutation, located in exon 7, substituted a glycine for an arginine at codon 269. Login to comment 88 ABCG5 p.Gly269Arg This new mutation, p.G269R, was not detected in 50 healthy controls. Login to comment