کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10834657 | 1065914 | 2007 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed by ALDH7A1 mutational analysis
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کلمات کلیدی
P6CALDH7A1 geneRT-PCR analysisRT-PCRGADPDSPLPγ-amino butyric acid - γ-آمینو اسید بوتیریکAlu repeats - آلو تکرار می کندpipecolic acid - اسید پپکولیکElectroencephalogram - الکتروانسفالوگرافیConvulsion - تحرکLymphoblasts - لنفوبلاست هاCSF - مایع مغزی نخاعیCerebrospinal fluid - مایع مغزی نخاعیGenetic heterogeneity - ناهمگنی ژنتیکیEEG - نوار مغزیVitamin B6 - ویتامین B6Pyridoxal phosphate - پرییدکسال فسفاتGABA - گاباGlutamate decarboxylase - گلوتامات دکربوکسیلاز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Pyridoxine dependent seizure (PDS) is a disorder of neonates or infants with autosomal recessive inheritance characterized by seizures, which responds to pharmacological dose of pyridoxine. Recently, mutations have been identified in the ALDH7A1 gene in Caucasian families with PDS. To elucidate further the genetic background of PDS, we screened for ALDH7A1 mutations in five PDS families (patients 1-5) that included four Orientals. Diagnosis as having PDS was confirmed by pyridoxine-withdrawal test. Exon sequencing analysis of patients 1-4 revealed eight ALDH7A1 mutations in compound heterozygous forms: five missense mutations, one nonsense mutation, one point mutation at the splicing donor site in intron 1, and a 1937-bp genomic deletion. The deletion included the entire exon 17, which was flanked by two Alu elements in introns 16 and 17. None of the mutations was found in 100 control chromosomes. In patient 5, no mutation was found by the exon sequencing analysis. Furthermore, expression level or nucleotide sequences of ALDH7A1 mRNA in lymphoblasts were normal. Plasma pipecolic acid concentration was not elevated in patient 5. These observations suggest that ALDH7A1 mutation is unlikely to be responsible for patient 5. Abnormal metabolism of GABA/glutamate in brain has long been suggested as the underlying pathophysiology of PDS. CSF glutamate concentration was elevated during the off- pyridoxine period in patient 3, but not in patient 2 or 5. These results suggest allelic and non-allelic heterogeneities of PDS, and that the CSF glutamate elevation does not directly correlate with the presence of ALDH7A1 mutations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 91, Issue 4, August 2007, Pages 384-389
Journal: Molecular Genetics and Metabolism - Volume 91, Issue 4, August 2007, Pages 384-389
نویسندگان
Junko Kanno, Shigeo Kure, Ayumi Narisawa, Fumiaki Kamada, Masaru Takayanagi, Katsuya Yamamoto, Hisao Hoshino, Tomohide Goto, Takao Takahashi, Kazuhiro Haginoya, Shigeru Tsuchiya, Fritz A.M. Baumeister, Yuki Hasegawa, Yoko Aoki, Seiji Yamaguchi,