Spiegel Ronen, Shaag Avraham, Shalev Stavit, Elpeleg Orly
Pediatric Department B, Emek Medical Center, Afula, Israel.
Rappaport faculty of Medicine, Technion, Haifa, Israel.
Neurogenetics. 2016 Jul;17(3):187-90. doi: 10.1007/s10048-016-0483-3. Epub 2016 Apr 28.
Febrile-induced neurodegenerative diseases are a heterogeneous group of genetic disorders most commonly inborn errors of metabolism that result in irreversible damage involving the central nervous system. Here, we report on five siblings of consanguineous family who developed normally for the first 6-12 months of life then presented with a severe leukoencephalopathy following a trivial febrile illness. Using homozygosity mapping followed by whole exome sequencing, we identified a homozygous c. 281C>A mutation in the APOA1BP gene resulting in substitution of a highly conserved alanine residue with aspartic acid (p.Ala94Asp). APOA1BP encodes for epimerase that catalyzes the R to S epimerization of NAD(P)XH, a crucial step in the dehydration of these toxic metabolites accumulating during cellular metabolism. This is the first report of a defect in the nicotinamide nucleotide repair system in humans.
发热诱导的神经退行性疾病是一组异质性的遗传疾病，最常见的是先天性代谢缺陷，会导致涉及中枢神经系统的不可逆损伤。在此，我们报告了一个近亲家庭的五名兄弟姐妹，他们在生命的最初6至12个月发育正常，随后在一次轻微的发热性疾病后出现严重的白质脑病。通过纯合性定位，随后进行全外显子组测序，我们在APOA1BP基因中鉴定出一个纯合的c.281C>A突变，导致一个高度保守的丙氨酸残基被天冬氨酸替代（p.Ala94Asp）。APOA1BP编码差向异构酶，该酶催化NAD(P)XH的R到S差向异构化，这是细胞代谢过程中积累的这些有毒代谢物脱水的关键步骤。这是人类烟酰胺核苷酸修复系统缺陷的首次报告。
