Abstract:
:Vitamin-B6-dependent epilepsies are a heterogenous group of treatable disorders due to mutations in several genes (ALDH7A1, PNPO, ALPL or ALDH4A1). In neonatal seizures, defects in ALDH7A1 and PNPO explain a major fraction of cases. Very recently biallelic mutations in PROSC were shown to be a novel cause in five families. We identified four further unrelated patients harbouring a total of six different mutations, including four novel disease mutations. Vitamin B6 plasma profiles on pyridoxine did not enable the differentiation of patients with PROSC mutations. All four patients were normocephalic and had normal cranial imaging. Pyridoxine monotherapy allowed complete seizure control in one, while two patients had occasional febrile or afebrile seizures and one needed additional valproate therapy for photosensitive seizures. Two patients underwent a controlled pyridoxine withdrawal with signs of encephalopathy within a couple of days. Three had favourable outcome with normal intellectual properties at age 12.5, 15.5 and 30 years, respectively, while one child had marked developmental delay at age 27 months. The clinical and electroencephalographic phenotype in patients with PROSC mutations was indistinguishable from ALDH7A1 and PNPO deficiency. We therefore confirm PROSC as a novel gene for vitamin-B6-dependent epilepsy and delineate a non-specific plasma vitamin B6 profile under pyridoxine treatment.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Plecko B,Zweier M,Begemann A,Mathis D,Schmitt B,Striano P,Baethmann M,Vari MS,Beccaria F,Zara F,Crowther LM,Joset P,Sticht H,Papuc SM,Rauch Adoi
10.1136/jmedgenet-2017-104521subject
Has Abstractpub_date
2017-12-01 00:00:00pages
809-814issue
12eissn
0022-2593issn
1468-6244pii
jmedgenet-2017-104521journal_volume
54pub_type
杂志文章abstract::Evidence is presented to support the recent suggestion that human neural tube closure is similar to that observed in mice, and comprises several regionally distinct closure sites rather than being a simple zipping up process. Seven subjects, each with more than one neural tube defect (NTD), are described. Comparative ...
journal_title:Journal of medical genetics
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doi:10.1136/jmg.32.3.205
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doi:10.1136/jmg.29.10.747
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pub_type: 杂志文章,多中心研究
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更新日期:2011-02-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 信件
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:2009-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2011-09-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2019-106474
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abstract::Recent epidemiological interest has focused on separation of neural tube defects (NTD) into subgroups which may differ pathogenetically and aetiologically, for example, 'upper' and 'lower' spina bifida. In order to validate the use of pathologists' lesion descriptions by epidemiologists and others, a postal survey of ...
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journal_title:Journal of medical genetics
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journal_title:Journal of medical genetics
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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journal_title:Journal of medical genetics
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