Identification and characterization of two novel mutations that produce acute intermittent porphyria: A 3-base deletion (841-843delGGA) and a missense mutation (T35M)

Identification and characterization of two novel mutations that produce acute intermittent porphyria: A 3-base deletion (841-843delGGA) and a missense mutation (T35M)

A partial deficiency of Porphobilinogen deaminase (PBGD) is responsible for acute intermittent porphyria (AIP). AIP is inherited in an autosomal dominant fashion, and the prevalence in the Argentinean population is about 1:125,000. Here, two new mutations and two previously reported were found in th...

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Bibliographic Details
Published in:Human mutation Vol. 16; no. 4; p. 373
Main Authors: Siervi, Adriana De, Cádiz, Débora E. Weiss, Parera, Victoria E., del C. Batlle, Alcira M., Rossetti, Maria Victoria
Format: Journal Article
Language:English
Published: New York John Wiley & Sons, Inc 01-10-2000
Hindawi Limited
Subjects:
acute intermittent porphyria
Adolescent
Adult
AIP
Child
Female
HMBS
Humans
hydroxymethylbilane synthase
Hydroxymethylbilane Synthase - genetics
Male
metabolic disorders
Methionine - genetics
Middle Aged
Mutation, Missense - genetics
PBGD
porphobilinogen deaminase
Porphyria, Acute Intermittent - enzymology
Porphyria, Acute Intermittent - genetics
porphyrins
Sequence Deletion - genetics
Threonine - genetics
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Summary:A partial deficiency of Porphobilinogen deaminase (PBGD) is responsible for acute intermittent porphyria (AIP). AIP is inherited in an autosomal dominant fashion, and the prevalence in the Argentinean population is about 1:125,000. Here, two new mutations and two previously reported were found in the PBGD gene in 22 Argentinean AIP patients corresponding to 8 different families. To screen for AIP mutations in symptomatic patients, genomic DNA isolated was amplified in 6 PCR reactions, then all coding exons and flanking intronic regions were sequenced. The novel mutations are 841‐843delGGA in exon 14, which results in the loss of glycine‐281 (G281del), and one 104C>T point mutation in the exon 4 (T35M). To further characterize both novel mutations, the pKK‐PBGD construct for the mutant alleles were expressed in E. coli, the enzymatic activity of the recombinant proteins were 1% and 4% of the mean level expressed by the normal allele for 841‐843delGGA and T35M, respectively. Hum Mutat 16:373, 2000. © 2000 Wiley‐Liss, Inc.
Bibliography:istex:5C0CF308799BFFCD1431273DA9CBFDC85488753D
ark:/67375/WNG-691V8X44-R
ArticleID:HUMU14
University of Buenos Aires (UBA), CONICET and the Science and Technology Agency - No. EX0032/95-98; No. 00509108/97; No. PICT 05-00000-01861
http://journals.wiley.com/1059‐7794/pdf/mutation/370.pdf
Human Mutation
Online Citation
Mutation in Brief #370 (2000) Online
Communicated by: Mark H. Paalman
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1059-7794
1098-1004
DOI:10.1002/1098-1004(200010)16:4<373::AID-HUMU14>3.0.CO;2-A