title: Acute intermittent porphyria: novel missense mutations in the human hydroxymethylbilane synthase gene.
abstract: OBJECTIVE
  To identify mutations in families with acute intermittent porphyria, an autosomal dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase.
  
  
  METHODS
  Mutations were identified by direct solid phase sequencing.
  
  
  RESULTS
  Two novel missense mutations E80G and T78P and three previously reported mutations, R173W, G111R, and the splice site lesion, IVS1+1, were detected, each in an unrelated proband. The causality of the novel missense mutations was demonstrated by expression studies.
  
  
  CONCLUSIONS
  These findings provide for the precise diagnosis of carriers in these families and further expand the molecular heterogeneity of AIP.
authors.affiliation: Departments of Human Genetic, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Ramdall
authors.forename: L
authors.initials: L
authors.lastname: Cunha
authors.forename: K H
authors.initials: KH
authors.lastname: Astrin
authors.forename: D R
authors.initials: DR
authors.lastname: Katz
authors.forename: K E
authors.initials: KE
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Glucksman
authors.forename: S S
authors.initials: SS
authors.lastname: Bottomley
authors.forename: R J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D019943:Amino Acid Substitution; D005260:Female; D015870:Gene Expression; D006418:Heme / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense; D017118:Porphyria, Acute Intermittent / Q000201:enzymology / Q000235:genetics*
chemical_list: D006418:Heme; D011163:Hydroxymethylbilane Synthase