Novel mutations in pyridoxine-dependent epilepsy

Millet, Anne; Salomons, Gajja S.; Cneude, F.; Corne, Christelle; Debillon, Thierry; Jakobs, Cornelis; Struys, Eduard A.; Hamelin, Sophie

doi:10.1016/j.ejpn.2010.03.011

Cited by 24 publications

(28 citation statements)

References 13 publications

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“…1 and previously reported mutations are referenced in Table 1 (Mills et al 2006; Plecko et al 2007; Salomons et al 2007; Kanno et al 2007; Kluger et al 2008; Kaczorowska et al 2008; Striano et al 2009; Bennett et al 2009; Gallagher et al 2009; Schmitt et al 2010; Millet et al 2010). There are 26 missense mutations, 13 of which cluster in exons 14, 15, and 16.…”

Section: Resultsmentioning

confidence: 99%

“…Forty-seven such cases were presented in a recent report from the North American Registry of pyridoxine-dependent epilepsy (groups 1 and 2 in Gospe 2002). A subset of these patients, which we call group 1, have normal developmental outcome, including our patient 1 (8 cases in Basura et al 2009; case C2 in Mills et al 2006; 7/28 cases in Haenggli et al 1991; 1 case in Kluger et al 2008; patient 2 in Striano et al 2009; 3/11 patients in Been et al 2005; 1/6 cases in RamachandranNair and Parameswaran 2005; 2/9 patients with elevated pipecolic acid in Plecko et al 2005; and 1 case in Millet et al 2010). In contrast, the majority of patients with complete seizure control have mild to moderate developmental delays; these we call group 2, which includes patients 2 and 3 reported here.…”

Section: Discussionmentioning

confidence: 99%

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The genotypic and phenotypic spectrum of pyridoxine‐dependent epilepsy due to mutations in ALDH7A1

Scharer

Brocker

Vasiliou

et al. 2010

J of Inher Metab Disea

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Pyridoxine-dependent epilepsy is a disorder associated with severe seizures that may be caused by deficient activity of α-aminoadipic semialdehyde dehydrogenase, encoded by the ALDH7A1 gene, with accumulation of α-aminoadipic semialdehyde and piperideine-6-carboxylic acid. The latter reacts with pyridoxal-phosphate, explaining the effective treatment with pyridoxine. We report the clinical phenotype of three patients, their mutations and those of 12 additional patients identified in our clinical molecular laboratory. There were six missense, one nonsense, and five splice-site mutations, and two small deletions. Mutations c.1217_1218delAT, I431F, IVS-1(+2)T>G, IVS-2(+1)G>A, and IVS-12(+1)G>A are novel. Some disease alleles were recurring: E399Q

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The genotypic and phenotypic spectrum of pyridoxine‐dependent epilepsy due to mutations in ALDH7A1

Scharer

Brocker

Vasiliou

et al. 2010

J of Inher Metab Disea

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“…More than 60 different mutations within the 18 exons of the ALDH7A1 gene have been published [5]–[12]. In this report, we describe 3 Chinese patients in whom genetic analysis revealed four novel mutations and one known mutation in the ALDH7A1 gene.…”

Section: Introductionmentioning

confidence: 89%

Clinical Diagnosis, Treatment, and ALDH7A1 Mutations in Pyridoxine-Dependent Epilepsy in Three Chinese Infants

Yang

et al. 2014

PLoS ONE

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Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder that causes seizures in neonates and infants. Mutations of the ALDH7A1 gene are now recognized as the molecular basis PDE and help to define this disease. Three Chinese children with PDE were clinically analyzed, followed by treatment and examination of the ALDH7A1 mutations. The seizures of the 3 patients were all resistant to multiple anticonvulsants (2 to 7 types). For case 1, onset of seizures was at the age of 2 months. His seizures were well controlled by intravenous pyridoxine for several days at the age of 3 months 20 days and recurred at intervals of 13, 14 and 38 days after pyridoxine withdrawn for 3 times. At the age of 7 months, symptoms of PDE appeared and uninterrupted oral pyridoxine started. For case 2, her seizures occurred at 8 days after birth. After administration of multiple antiepileptic drugs observed ineffective, high-dose pyridoxine continuous therapy was taken at the age of 10 months and the significant treatment effect induced a diagnostic PDE. Seizure onset in case 3 was at the first day of birth. He experienced inadvertently pyridoxine therapy several times (first time at 2 days after birth) and achieved good therapeutic effect, which was confirmed by physicians until 4 months 10 days. The treatment process in our 3 patients suggested that pyridoxine should be early and purposefully used in patients with early onset seizures. ALDH7A1 gene mutation analysis revealed compound heterozygous mutations in each case: heterozygous c.410G>A (p.G137E) and IVS11+1G>A in case 1, heterozygous c.952G>C (p.A318P) and heterozygous c.965C>T (p.A322V) in case 2, and heterozygous c.902A>T (p.N301I) and IVS11+1G>A in case 3. Only p.N301I was reported previously, all other mutations were novel. This is the first time to report cases of Chinese patients diagnosed with PDE by molecular genetic analysis.

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“…The dependence is permanent, and the interruption of daily pyridoxine supplementation leads to recurrence of seizures. Four clinical criteria are used to establish the right PDE diagnosis: seizures resistant to standard antiepileptic drugs, good response to pyridoxine, complete seizure control on pyridoxine monotherapy, and seizure recurrence after pyridoxine withdrawal [1]. Some patients show developmental delay.…”

Section: Introductionmentioning

confidence: 99%

First cases of pyridoxine-dependent epilepsy in Bulgaria: novel mutation in the ALDH7A1 gene

et al. 2015

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Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder characterized by intractable seizures in neonates and infants. The seizures cannot be controlled with antiepileptic medications but respond both clinically and electrographically to large daily supplements of pyridoxine (vitamin B6). PDE is caused by mutations in the ALDH7A1 gene. Molecular genetic analysis of the ALDH7A1 gene was performed in seven patients, referred with clinical diagnosis of PDE. Mutations were detected in a dizygotic twin pair and a non-related boy with classical form of PDE. Direct sequencing of the ALDH7A1 gene revealed one novel (c.297delG, p.Trp99*) and two already reported (c.328C>T, p.Arg110*; c.584A>G, p.Asn195Ser) mutations. Here, we report the first genetically proven cases of PDE in Bulgaria.

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Novel mutations in pyridoxine-dependent epilepsy

Cited by 24 publications

References 13 publications

The genotypic and phenotypic spectrum of pyridoxine‐dependent epilepsy due to mutations in ALDH7A1

The genotypic and phenotypic spectrum of pyridoxine‐dependent epilepsy due to mutations in ALDH7A1

Clinical Diagnosis, Treatment, and ALDH7A1 Mutations in Pyridoxine-Dependent Epilepsy in Three Chinese Infants

First cases of pyridoxine-dependent epilepsy in Bulgaria: novel mutation in the ALDH7A1 gene

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