Mutations in antiquitin in individuals with pyridoxine-dependent seizures

被引：392

作者：

Mills, PB

Struys, E

Jakobs, C

Plecko, B

Baxter, P

Baumgartner, M

Willemsen, MAAP

Omran, H

Tacke, U

Uhlenberg, B

Weschke, B

Clayton, PT

机构：

[1] UCL, Great Ormond St Hosp Children Children, Natl Hlth Serv Trust, Inst Child Hlth, London, England

[2] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Metab Unit, NL-1081 HV Amsterdam, Netherlands

[3] Univ Hosp Graz, Dept Pediat, A-8036 Graz, Austria

[4] Sheffields Childrens Hosp, Sheffield S10 2TH, S Yorkshire, England

[5] Univ Childrens Hosp, Div Metab & Mol Pediat, CH-8032 Zurich, Switzerland

[6] Univ Nijmegen, Med Ctr, Dept Pediat Neurol, NL-6500 HB Nijmegen, Netherlands

[7] Univ Freiburg, Dept Neuropediat, D-79106 Freiburg, Germany

[8] Charite Univ Med Berlin, Dept Neuropediat, D-13353 Berlin, Germany

来源：

NATURE MEDICINE | 2006年 / 12卷 / 03期

关键词：

D O I：

10.1038/nm1366

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：

We show here that children with pyridoxine-dependent seizures (PDS) have mutations in the ALDH7A1 gene, which encodes antiquitin; these mutations abolish the activity of antiquitin as a Delta(1)-piperideine-6-carboxylate (P6C)-alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase. The accumulating P6C inactivates pyridoxal 5'-phosphate (PLP) by forming a Knoevenagel condensation product. Measurement of urinary alpha-AASA provides a simple way of confirming the diagnosis of PDS and ALDH7A1 gene analysis provides a means for prenatal diagnosis.

引用

页码：307 / 309

页数：3

共 16 条

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