TY - CHAP
T1 - Seven novel mutations in bulgarian patients with acute hepatic porphyrias (AHP)
AU - Dragneva, Sonya
AU - Szyszka-Niagolov, Monika
AU - Ivanova, Aneta
AU - Mateva, Lyudmila
AU - Izumi, Rumiko
AU - Aoki, Yoko
AU - Matsubara, Yoichi
N1 - Funding Information:
Acknowledgements We would like to thank all of the families that participated in this study. We would also like to gratefully acknowledge Prof. Dimcho Adjarov for the fruitful discussions and suggestions, as well as for supplying the clinical and biochemical data used in this study. Mrs. Doroteya Leonkeva, Mrs. Kumi Kato, and Ms. Yoko Tateda are also gratefully acknowledged for their skillful technical assistance. We acknowledge the support from Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)
PY - 2014
Y1 - 2014
N2 - Acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP) are caused by mutations in the hydroxymethylbilane synthase (HMBS), protoporphyrinogen oxidase (PPOX), and coproporphyrinogen oxidase (CPOX) genes, respectively. This study aimed to identify mutations in seven Bulgarian families with AIP, six with VP, and one with HCP. A total of 33 subjects, both symptomatic (n = 21) and asymptomatic (n = 12), were included in this study. The identification of mutations was performed by direct sequencing of all the coding exons of the corresponding enzymes in the probands. The available relatives were screened for the possible mutations. A total of six different mutations in HMBS were detected in all seven families with AIP, three of which were previously described: c.76C>T [p.R26C] in exon 3, c.287C>T [p.S96F] in exon 7, and c.445C>T [p.R149X] in exon 9. The following three novel HMBS mutations were found: c.345-2A>C in intron 7–8, c.279-280insAT in exon 7, and c.887delC in exon 15. A total of three different novel mutations were identified in the PPOX gene in the VP families: c.441-442delCA in exon 5, c.917T>C [p.L306P] in exon 9, and c.1252T>C [p.C418R] in exon 12. A novel nonsense mutation, c.364G>T [p.E122X], in exon 1 of the CPOX gene was identified in the HCP family. This study, which identified mutations in Bulgarian families with AHP for the first time, established seven novel mutation sites. Seven latent carriers were also diagnosed and, therefore, were able to receive crucial counseling to prevent attacks.
AB - Acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP) are caused by mutations in the hydroxymethylbilane synthase (HMBS), protoporphyrinogen oxidase (PPOX), and coproporphyrinogen oxidase (CPOX) genes, respectively. This study aimed to identify mutations in seven Bulgarian families with AIP, six with VP, and one with HCP. A total of 33 subjects, both symptomatic (n = 21) and asymptomatic (n = 12), were included in this study. The identification of mutations was performed by direct sequencing of all the coding exons of the corresponding enzymes in the probands. The available relatives were screened for the possible mutations. A total of six different mutations in HMBS were detected in all seven families with AIP, three of which were previously described: c.76C>T [p.R26C] in exon 3, c.287C>T [p.S96F] in exon 7, and c.445C>T [p.R149X] in exon 9. The following three novel HMBS mutations were found: c.345-2A>C in intron 7–8, c.279-280insAT in exon 7, and c.887delC in exon 15. A total of three different novel mutations were identified in the PPOX gene in the VP families: c.441-442delCA in exon 5, c.917T>C [p.L306P] in exon 9, and c.1252T>C [p.C418R] in exon 12. A novel nonsense mutation, c.364G>T [p.E122X], in exon 1 of the CPOX gene was identified in the HCP family. This study, which identified mutations in Bulgarian families with AHP for the first time, established seven novel mutation sites. Seven latent carriers were also diagnosed and, therefore, were able to receive crucial counseling to prevent attacks.
KW - Acute intermittent porphyria
KW - Acute intermittent porphyria
KW - Hereditary coproporphyria
KW - Protoporphyrinogen oxidase
KW - Variegate porphyria
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U2 - 10.1007/8904_2014_320
DO - 10.1007/8904_2014_320
M3 - Chapter
AN - SCOPUS:85060275338
T3 - JIMD Reports
SP - 57
EP - 64
BT - JIMD Reports
PB - Springer
ER -