HMBS mutations in chinese patients with acute intermittent porphyria
Journal
Annals of Human Genetics
Journal Volume
72
Journal Issue
5
Pages
683-686
ISSN
1469-1809
Date Issued
2008
Author(s)
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. ? 2008 The Authors Journal compilation ? 2008 Blackwell Publishing Ltd/University College London.
SDGs
Other Subjects
arginine; asparagine; drug; glycine; heme; hormone; porphobilinogen deaminase; proline; abdominal pain; acute intermittent porphyria; adolescent; adult; allele; article; autosomal dominant disorder; Chinese; clinical article; controlled study; diet restriction; disease association; enzyme deficiency; family study; female; frameshift mutation; gene mutation; genetic disorder; heme synthesis; human; male; missense mutation; nonsense mutation; paresis; phenotype; priority journal; recurrent disease; Taiwan; urine color; Adolescent; Adult; Asian Continental Ancestry Group; Base Sequence; DNA; DNA Mutational Analysis; Female; Humans; Hydroxymethylbilane Synthase; Male; Mutation; Porphyria, Acute Intermittent; Taiwan
Type
journal article