Identification of a novel missense mutation in the ALDH7A1 gene in two unrelated Tunisian families with pyridoxine-dependent epilepsy

被引：5

作者：

Tlili, Abdelaziz ^{[1
]}

Hentati, Nadia Hamida ^{[2
]}

Gargouri, Abdellatif ^{[2
]}

Fakhfakh, Faiza ^{[1
]}

机构：

[1] Univ Sfax, Fac Med Sfax, Lab Genet Mole Humaine, Sfax 3029, Tunisia

[2] CHU Hedi Chaker Sfax, Serv Neonatol, Sfax, Tunisia

来源：

MOLECULAR BIOLOGY REPORTS | 2013年 / 40卷 / 01期

关键词：

Pyridoxine-dependent epilepsy; ALDH7A1; Novel pathogenic variant; Computing analysis; SEIZURES; ANTIQUITIN;

D O I：

10.1007/s11033-012-2084-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pyridoxine-dependent Epilepsy (PDE) is a rare autosomal recessive disorder causing intractable seizures in neonates and infants. It is characterized by seizures that are resistant to common anticonvulsants, but patients respond well to the administration of pyridoxine. PDE is caused by ALDH7A1 genetic defect. Here, we report the disease-causative variant in the ALDH7A1 gene in two affected Tunisian families. Direct sequencing analysis revealed a novel missense mutation c.1364T > C (p.Leu455Pro). Using bioinformatic tools we suggested that this variant may have deleterious effects on ALDH7A1 protein structure and function.

引用

页码：487 / 490

页数：4

共 11 条

[1] A method and server for predicting damaging missense mutations [J].

Adzhubei, Ivan A. ;

Schmidt, Steffen ;

Peshkin, Leonid ;

Ramensky, Vasily E. ;

Gerasimova, Anna ;

Bork, Peer ;

Kondrashov, Alexey S. ;

Sunyaev, Shamil R. .

NATURE METHODS, 2010, 7 (04) :248-249

[2] Pyridoxine-dependent and pyridoxine-responsive seizures [J].

Baxter, P .

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY, 2001, 43 (06) :416-420

[3] Pyridoxine-dependent seizures: a clinical and biochemical conundrum [J].

Baxter, P .

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2003, 1647 (1-2) :36-41

[4] Genetic heterogeneity for autosomal recessive pyridoxine-dependent seizures [J].

Bennett, CL ;

Huynh, HM ;

Chance, PF ;

Glass, IA ;

Gospe, SM .

NEUROGENETICS, 2005, 6 (03) :143-149

[5] A gene for pyridoxine-dependent epilepsy maps to chromosome 5q31. [J].

Comier-Daire, V ;

Dragoneau, N ;

Burglen, L ;

Munnich, AN ;

Dulac, O .

AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (04) :20-20

[6] Pyridoxine-dependent seizures: new genetic and biochemical clues to help with diagnosis and treatment [J].

Gospe, SM .

CURRENT OPINION IN NEUROLOGY, 2006, 19 (02) :148-153

[7] Mutations in antiquitin in individuals with pyridoxine-dependent seizures [J].

Mills, PB ;

Struys, E ;

Jakobs, C ;

Plecko, B ;

Baxter, P ;

Baumgartner, M ;

Willemsen, MAAP ;

Omran, H ;

Tacke, U ;

Uhlenberg, B ;

Weschke, B ;

Clayton, PT .

NATURE MEDICINE, 2006, 12 (03) :307-309

[8] Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency) [J].

Mills, Philippa B. ;

Footitt, Emma J. ;

Mills, Kevin A. ;

Tuschl, Karin ;

Aylett, Sarah ;

Varadkar, Sophia ;

Hemingway, Cheryl ;

Marlow, Neil ;

Rennie, Janet ;

Baxter, Peter ;

Dulac, Olivier ;

Nabbout, Rima ;

Craigen, William J. ;

Schmitt, Bernhard ;

Feillet, Francois ;

Christensen, Ernst ;

De Lonlay, Pascale ;

Pike, Mike G. ;

Hughes, M. Imelda ;

Struys, Eduard A. ;

Jakobs, Cornelis ;

Zuberi, Sameer M. ;

Clayton, Peter T. .

BRAIN, 2010, 133 :2148-2159

[9] Predicting deleterious amino acid substitutions [J].

Ng, PC ;

Henikoff, S .

GENOME RESEARCH, 2001, 11 (05) :863-874

[10] Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene [J].

Plecko, Barbara ;

Paul, Karl ;

Paschke, Eduard ;

Stoeckler-Ipsiroglu, Sylvia ;

Struys, Eduard ;

Jakobs, Cornelis ;

Hartmann, Hans ;

Luecke, Thomas ;

di Capua, Matteo ;

Korenke, Christoph ;

Hikel, Christiane ;

Reutershahn, Elke ;

Freilinger, Michael ;

Baumeister, Fritz ;

Bosch, Friedrich ;

Erwa, Wolfgang .

HUMAN MUTATION, 2007, 28 (01) :19-26

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