title: HMBS mutations in Chinese patients with acute intermittent porphyria.
abstract: Acute intermittent porphyria (AIP), an autosomal dominant disorder, is caused by partial deficiency of hydroxymethylbilane synthase (HMBS) affecting heme biosynthesis. Patients with AIP are characterized by recurrent abdominal pain, port-wine urine, and motor paresis. The disease can be provoked by changes in hormone levels, drugs and fasting. Molecular analysis for twenty-four unrelated Chinese AIP patients from Taiwan identified twenty-five HMBS mutations. There were 10 missense (40%), four nonsense (16%), five frame-shift (20%) and six splice site (24%) mutations. More than a half (15/25, 60%) of these mutations are predicted to produce a truncated protein. Four (c.33 + 5C>A, Arg26Cys, Arg26His, Arg325X) occurred more than once among the 24 families and one individual carried two mutations in the same allele, a missense (Gly221Asp) and a splice site mutation (c.652-1G>A). Of the 25 mutations, eleven were novel (Arg149Pro, Gly218Arg, Asn322X, Gly221Asp, Pro313X, c.88-4_-16delAAGTCTCTACCCG, c.1008_1019delCAGCCTGGCCAA, c.113delT, c.88-4_-16delAAGTCTCTACCCGinsCA, c.160delA, c.902_909delTCCCTGCC). No correlation between genetic defect and phenotype (both clinical and biochemical) was observed in this study.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, National Taiwan University School of Medicine, Taipei, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Yang
authors.forename: H-C
authors.initials: HC
authors.lastname: Kuo
authors.forename: H-L
authors.initials: HL
authors.lastname: You
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: C-C
authors.initials: CC
authors.lastname: Huang
authors.forename: C-Y
authors.initials: CY
authors.lastname: Liu
authors.forename: M-Y
authors.initials: MY
authors.lastname: Lan
authors.forename: D A
authors.initials: DA
authors.lastname: Stephenson
authors.forename: M-J
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics*; D008297:Male; D009154:Mutation; D017118:Porphyria, Acute Intermittent / Q000201:enzymology* / Q000235:genetics*; D013624:Taiwan
chemical_list: D004247:DNA; D011163:Hydroxymethylbilane Synthase