Identification and characterization of 40 novel hydroxymethylbilane synthase mutations that cause acute intermittent porphyria.

ABSTRACT: Acute intermittent porphyria (AIP), an autosomal dominant disorder due to the half-normal activity of hydroxymethylbilane synthase (HMBS), is characterized by acute neurovisceral attacks that are precipitated by factors that induce heme biosynthesis. Molecular diagnosis is the most sensitive and specific diagnostic test for AIP, and importantly, it permits the identification of asymptomatic family members for genetic counseling and avoidance of precipitating factors. Here, we report the identification of 40 novel HMBS mutations, including 11 missense, four nonsense, 16 small insertions or deletions, eight consensus splice site mutations, and a complex insertion-deletion mutation in unrelated individuals with AIP. Prokaryotic expression of the missense mutations demonstrated that all mutant

SUBMITTER: Chen B 

PROVIDER: S-EPMC6162174 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature