Open AccessPorphobilmogen deaminase gene mutations in Brazilian acute intermittent porphyria patients
Author(s) -
Ribeiro Georgina Severo,
Marchiori Paulo Eurípedes,
Kuntz Puglia Paula Marzorati,
Nagai Maria Aparecida,
dos Santos Mariana Lopes,
oyama Kimiyo,
Hirata Mário Hiroyuki,
Barretto Orlando C.O.
Publication year - 2002
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.10053
Subject(s) - exon , acute intermittent porphyria , missense mutation , genetics , single strand conformation polymorphism , intron , biology , nonsense mutation , microbiology and biotechnology , porphobilinogen deaminase , mutation , gene , gene mutation , porphyria , endocrinology
Acute intermittent porphyria (AIP) is an autosomal dominant disorder resulting from porphobilmogen deaminase (PBGD) deficiency. Seven unrelated Brazilian patients were investigated regarding PBGD gene mutations by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing. The PBG gene screening disclosed abnormal SSCP patterns in exons 7, 9, 12, 13, and 15, as well as in introns 3 and 10. Direct DNA sequencing revealed the occurrence of three nonsense mutations (R149X, R225X, and R325X) in exons 9, 12, and 15, respectively, and one missense mutation G111R in exon 7. The G111R mutation was detected in two unrelated patients. Intragenic polymorphisms (3119G/T in intron 2, 3581G/A in intron 3, 7052A/G and 7064C/A in intron 10, and −65C/T in exon 1) were also observed. In addition, two silent mutations (V202V in exon 10 and A266A in exon 13) were found. The latter has not heretofore been reported. Thus, this study revealed the mutations involved in Brazilian symptomatic AIP patients, as well as the intragenic polymorphisms found in the patients. J. Clin. Lab. Anal. 16:259–265, 2002. © 2002 Wiley‐Liss, Inc.