The genotypic spectrum of ALDH7A1 mutations resulting in pyridoxine dependent epilepsy: A common epileptic encephalopathy

Journal of Inherited Metabolic Disease
Curtis R CoughlinJohan L K Van Hove

Abstract

Pyridoxine dependent epilepsy (PDE) is a treatable epileptic encephalopathy characterized by a positive response to pharmacologic doses of pyridoxine. Despite seizure control, at least 75% of individuals have intellectual disability and developmental delay. Current treatment paradigms have resulted in improved cognitive outcomes emphasizing the importance of an early diagnosis. As genetic testing is increasingly accepted as first tier testing for epileptic encephalopathies, we aimed to provide a comprehensive overview of ALDH7A1 mutations that cause PDE. The genotypes, ethnic origin and reported gender was collected from 185 subjects with a diagnosis of PDE. The population frequency for the variants in this report and the existing literature were reviewed in the Genome Aggregation Database (gnomAD). Novel variants identified in population databases were also evaluated through in silico prediction software and select variants were over-expressed in an E.coli-based expression system to measure α-aminoadipic semialdehyde dehydrogenase activity and production of α-aminoadipic acid. This study adds 47 novel variants to the literature resulting in a total of 165 reported pathogenic variants. Based on this report, in silico prediction...Continue Reading

References

Jun 4, 1999·The Journal of Pediatrics·M EbingerS König
Oct 16, 1999·Archives of Disease in Childhood·P Baxter
Sep 15, 2005·Archives of Disease in Childhood·J V BeenW O Renier
Feb 24, 2006·Nature Medicine·Philippa B MillsPeter T Clayton
Aug 28, 2007·Annals of Neurology·Gajja S SalomonsCornelis Jakobs
Jun 18, 2010·Brain : a Journal of Neurology·Philippa B MillsPeter T Clayton
Sep 4, 2010·Journal of Inherited Metabolic Disease·Gunter ScharerJohan L K Van Hove
Jul 19, 2012·Developmental Medicine and Child Neurology·Levinus A BokMichèl A Willemsen
Oct 2, 2012·Molecular Genetics and Metabolism·Clara D M van KarnebeekSylvia Stockler
Aug 16, 2014·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Saadet Mercimek-MahmutogluEva Mamak
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Mar 21, 2016·Pediatric Neurology·Clara D M van KarnebeekSylvia Stockler-Ipsiroglu
Jul 1, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Curtis R CoughlinJohan L K Van Hove
Nov 25, 2016·Metabolic Brain Disease·Amal Al TeneijiSaadet Mercimek-Mahmutoglu
Dec 3, 2016·American Journal of Human Genetics·Niklas DarinPeter T Clayton
Jan 15, 2017·Chemico-biological Interactions·David A KorasickMichael T Henzl
Apr 10, 2017·Journal of Medical Genetics·Barbara PleckoAnita Rauch
Sep 9, 2017·American Journal of Human Genetics·Lea M StaritaDouglas M Fowler

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Citations

Nov 19, 2019·Developmental Medicine and Child Neurology·Xianru JiaoZhixian Yang

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